Is COG7 p.Ala29Pro (c.85G>C) pathogenic?

COG7 p.Ala29Pro (c.85G>C) is classified Uncertain significance in COG7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). AlphaMissense: likely benign (0.1082); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with COG7 p.Ala29Pro (c.85G>C)?

COG7 p.Ala29Pro (c.85G>C) is associated with Inborn genetic diseases (ClinVar).

How common is COG7 p.Ala29Pro (c.85G>C) in the general population?

COG7 p.Ala29Pro (c.85G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about COG7 p.Ala29Pro (c.85G>C)?

AlphaMissense predicts likely benign (score 0.1082) — an in-silico prediction, not a clinical call.

COG7 p.Ala29Pro

c.85G>C · VCV3494993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1082 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1082	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -8.24	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 1.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 64 kb · p 0.033 · regional, not allelic
Overall
CADD	17.78	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 8.47e-05% European (non-Finnish) · 1/1,180,010 alleles

Overall 0.000657% 1/152,242 alleles · very rare

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: COG7
Protein: p.Ala29Pro
Coding: c.85G>C
MANE Select: NM_153603
Type: single nucleotide variant
Location: chr16:23452910 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.77

Full COG7 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

COG7 p.Ala29Val Uncertain significance ★★ ⚠ same residue
COG7 p.Ala20Val Uncertain significance ★★ ⚠ same condition
COG7 p.Ala37Thr Uncertain significance ★★ ⚠ same condition
COG7 p.Ala570Val Uncertain significance ★★ ⚠ same condition
COG7 p.Ala658Gly Uncertain significance ★★ ⚠ same condition
COG7 p.Arg480Trp Uncertain significance ★★ ⚠ same condition
COG7 p.Arg589Cys Uncertain significance ★★ ⚠ same condition
COG7 p.Arg731His 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/cog7-p-ala29pro (accessed [today's date]).

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