Is COMMD10 p.Ala59Val (c.176C>T) pathogenic?

COMMD10 p.Ala59Val (c.176C>T) is classified Likely benign in COMMD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-07). AlphaMissense: likely benign (0.0705); Very rare (popmax 0.0095%, nfe).

How common is COMMD10 p.Ala59Val (c.176C>T) in the general population?

COMMD10 p.Ala59Val (c.176C>T) is very rare (popmax 0.0095%, nfe) (gnomAD).

What do computational predictors say about COMMD10 p.Ala59Val (c.176C>T)?

AlphaMissense predicts likely benign (score 0.0705) — an in-silico prediction, not a clinical call.

COMMD10 p.Ala59Val

c.176C>T · rs146111323 · VCV2379914

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0705 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0095%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0705	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -6.91	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 0.82	GERP -0.73, phastCons 0.29
Regional constraint	o/e 1.33	unconstrained · MANE · 207 kb · p 5.3e-07 · regional, not allelic
Overall
CADD	13.15	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 0.0095% European (non-Finnish) · 112/1,178,618 alleles

Filtering AF 0.00805% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00753%

Overall 0.00807% 130/1,611,370 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0144%	6,930
European (non-Finnish)grpmax	0.0095%	10,523
African / African-American	0.00803%	12,458
Admixed American	0.00335%	29,850
South Asian	0.0011%	90,700

Remaining individuals 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: COMMD10
Protein: p.Ala59Val
Coding: c.176C>T
MANE Select: NM_016144
dbSNP: rs146111323
Type: single nucleotide variant
Location: chr5:116091122 (GRCh38)
Gene constraint: LOEUF 1.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.19 · 6 PDB
Residue 59: an α-helix

Full COMMD10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD10 p.Ala196Thr Uncertain significance ★ ⚠ same type
COMMD10 p.Ala2Pro Uncertain significance ★ ⚠ same type
COMMD10 p.Ala5Thr Uncertain significance ★ ⚠ same type
COMMD10 p.Ala90Val Uncertain significance ★ ⚠ same type
COMMD10 p.Arg125Gln Uncertain significance ★ ⚠ same type
COMMD10 p.Arg125Trp Uncertain significance ★ ⚠ same type
COMMD10 p.Arg36Trp Uncertain significance ★ ⚠ same type
COMMD10 p.Asn166Lys 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/commd10-p-ala59val (accessed [today's date]).

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