Is COG5 p.Ser801Pro (c.2401T>C) pathogenic?

COG5 p.Ser801Pro (c.2401T>C) is classified Conflicting classifications of pathogenicity in COG5 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-30). AlphaMissense: likely pathogenic (0.9279); Ultra-rare (popmax 0.065%, amr); Associated with Inborn genetic diseases.

What condition is associated with COG5 p.Ser801Pro (c.2401T>C)?

COG5 p.Ser801Pro (c.2401T>C) is associated with Inborn genetic diseases, COG5-congenital disorder of glycosylation (ClinVar).

How common is COG5 p.Ser801Pro (c.2401T>C) in the general population?

COG5 p.Ser801Pro (c.2401T>C) is ultra-rare (popmax 0.065%, amr) (gnomAD).

What do computational predictors say about COG5 p.Ser801Pro (c.2401T>C)?

AlphaMissense predicts likely pathogenic (score 0.9279) — an in-silico prediction, not a clinical call.

COG5 p.Ser801Pro

c.2401T>C · rs141942249 · VCV358451

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9279 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.065%, amr)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9279	likely pathogenic · top 10% in COG5
REVEL	0.212	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.58, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 360 kb · p 0.0042 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S811P vs ClinVar S801P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.065% Admixed American · 39/60,016 alleles

Filtering AF 0.0488% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0432%

Overall 0.0196% 317/1,613,838 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.564%	177
Admixed Americangrpmax	0.065%	1,539
Remaining individualsnot grpmax-eligible	0.0608%	1,644
Middle Eastern	0.0165%	6,078
European (non-Finnish)	0.00568%	17,609
South Asian	0.00329%	30,364
African / African-American	0.00267%	37,472

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: COG5
Protein: p.Ser801Pro
Coding: c.2401T>C
MANE Select: NM_006348
dbSNP: rs141942249
Type: single nucleotide variant
Location: chr7:107203605 (GRCh38)
Gene constraint: LOEUF 1.026 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.37

Full COG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: COG5-congenital disorder of glycosylation

Similar variants

COG5 c.1475+1G>A Likely pathogenic ★★ same condition
COG5 c.2295+2T>C Pathogenic/Likely pathogenic ★★ same condition
COG5 p.Arg205Ter Pathogenic ★★ same condition
COG5 p.Arg283Ter Pathogenic ★★ same condition
COG5 p.Arg461Ter Pathogenic/Likely pathogenic ★★ same condition
COG5 p.Arg690Ter Pathogenic/Likely pathogenic ★★ same condition
COG5 p.Arg708Ter Pathogenic/Likely pathogenic ★★ same condition
COG5 p.Met1Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cog5-p-ser801pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown