Is COG5 p.Pro472Leu (c.1415C>T) pathogenic?

COG5 p.Pro472Leu (c.1415C>T) is classified Uncertain significance in COG5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-04). AlphaMissense: likely benign (0.0947); Rare (popmax 0.102%, sas); Associated with Inborn genetic diseases.

What condition is associated with COG5 p.Pro472Leu (c.1415C>T)?

COG5 p.Pro472Leu (c.1415C>T) is associated with Inborn genetic diseases, COG5-congenital disorder of glycosylation (ClinVar).

How common is COG5 p.Pro472Leu (c.1415C>T) in the general population?

COG5 p.Pro472Leu (c.1415C>T) is rare (popmax 0.102%, sas) (gnomAD).

What do computational predictors say about COG5 p.Pro472Leu (c.1415C>T)?

AlphaMissense predicts likely benign (score 0.0947) — an in-silico prediction, not a clinical call.

COG5 p.Pro472Leu

c.1415C>T · rs143591444 · VCV1369541

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0947 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.102%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0947	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -7.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 360 kb · p 0.0042 · regional, not allelic
Overall
CADD	20.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P503L vs ClinVar P472L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.102% South Asian · 93/91,072 alleles

Filtering AF 0.0853% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0791%

Overall 0.00861% 139/1,613,520 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.102%	979
Middle Eastern	0.0822%	1,216
Remaining individualsnot grpmax-eligible	0.0096%	10,411
African / African-American	0.00401%	24,955
European (non-Finnish)	0.00263%	38,055
Admixed American	0.00167%	59,968

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.Pro472Leu
Coding: c.1415C>T
MANE Select: NM_006348
dbSNP: rs143591444
Type: single nucleotide variant
Location: chr7:107283631 (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 p.Pro472= Likely benign ★ same residue
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

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-pro472leu (accessed [today's date]).

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