Is COG3 p.Val792Ile (c.2374G>A) pathogenic?

COG3 p.Val792Ile (c.2374G>A) is classified Uncertain significance in COG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-09). AlphaMissense: likely benign (0.0759); Rare (popmax 0.156%, nfe).

How common is COG3 p.Val792Ile (c.2374G>A) in the general population?

COG3 p.Val792Ile (c.2374G>A) is rare (popmax 0.156%, nfe) (gnomAD).

What do computational predictors say about COG3 p.Val792Ile (c.2374G>A)?

AlphaMissense predicts likely benign (score 0.0759) — an in-silico prediction, not a clinical call.

COG3 p.Val792Ile

c.2374G>A · rs150980454 · VCV3147098

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0759 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.156%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0759	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 3.8	GERP 0.4, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 43 kb · p 4.3e-11 · regional, not allelic
Overall
CADD	20.4	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.156% European (non-Finnish) · 1,836/1,173,196 alleles

Filtering AF 0.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.148%

Overall 0.121% 1,944/1,606,348 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.156%	639
Remaining individualsnot grpmax-eligible	0.119%	841
African / African-American	0.0281%	3,557
Middle Eastern	0.0165%	6,064
Finnishnot grpmax-eligible	0.0125%	7,996
Admixed American	0.00667%	14,999

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: COG3
Protein: p.Val792Ile
Coding: c.2374G>A
MANE Select: NM_031431
dbSNP: rs150980454
Type: single nucleotide variant
Location: chr13:45530697 (GRCh38)
Gene constraint: LOEUF 0.314 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.82

Full COG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COG3 p.Ala14Val Uncertain significance ★ ⚠ same type
COG3 p.Ala190Gly Uncertain significance ★ ⚠ same type
COG3 p.Ala227Asp Uncertain significance ★ ⚠ same type
COG3 p.Ala227Thr Uncertain significance ★ ⚠ same type
COG3 p.Ala2Val Uncertain significance ★ ⚠ same type
COG3 p.Ala302Gly Uncertain significance ★ ⚠ same type
COG3 p.Ala364Ser Uncertain significance ★ ⚠ same type
COG3 p.Ala482Val Uncertain significance ★ ⚠ same type

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/cog3-p-val792ile (accessed [today's date]).

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