Is COG1 p.Arg404Gln (c.1211G>A) pathogenic?

COG1 p.Arg404Gln (c.1211G>A) is classified Likely benign in COG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-15). AlphaMissense: likely benign (0.0568); Very rare (popmax 0.00667%, amr); Associated with Inborn genetic diseases.

What condition is associated with COG1 p.Arg404Gln (c.1211G>A)?

COG1 p.Arg404Gln (c.1211G>A) is associated with Inborn genetic diseases (ClinVar).

How common is COG1 p.Arg404Gln (c.1211G>A) in the general population?

COG1 p.Arg404Gln (c.1211G>A) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about COG1 p.Arg404Gln (c.1211G>A)?

AlphaMissense predicts likely benign (score 0.0568) — an in-silico prediction, not a clinical call.

COG1 p.Arg404Gln

c.1211G>A · VCV4004815

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0568 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0568	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -5.17	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 -0.33	GERP -2.9
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.052 · regional, not allelic
Overall
CADD	2.929	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,990 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.0039% 63/1,613,918 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,997
European (non-Finnish)	0.00475%	21,071
Remaining individualsnot grpmax-eligible	0.0032%	31,239
South Asian	0.0011%	91,080

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: COG1
Protein: p.Arg404Gln
Coding: c.1211G>A
MANE Select: NM_018714
Type: single nucleotide variant
Location: chr17:73200706 (GRCh38)
Gene constraint: LOEUF 0.718 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.82

Full COG1 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

Similar variants

COG1 p.Ala209Val Uncertain significance ★★ ⚠ same condition
COG1 p.Ala27Ser Uncertain significance ★★ ⚠ same condition
COG1 p.Ala380Val Uncertain significance ★★ ⚠ same condition
COG1 p.Ala385Thr Uncertain significance ★★ ⚠ same condition
COG1 p.Ala563Val Uncertain significance ★★ ⚠ same condition
COG1 p.Arg165Gln Uncertain significance ★★ ⚠ same condition
COG1 p.Arg172Trp Uncertain significance ★★ ⚠ same condition
COG1 p.Arg178Gln Uncertain significance ★★ ⚠ 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/cog1-p-arg404gln (accessed [today's date]).

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