Is COMMD9 p.Ala57Ser (c.169G>T) pathogenic?

COMMD9 p.Ala57Ser (c.169G>T) is classified Uncertain significance in COMMD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.132); Very rare (popmax 0.00113%, sas).

How common is COMMD9 p.Ala57Ser (c.169G>T) in the general population?

COMMD9 p.Ala57Ser (c.169G>T) is very rare (popmax 0.00113%, sas) (gnomAD).

What do computational predictors say about COMMD9 p.Ala57Ser (c.169G>T)?

AlphaMissense predicts likely benign (score 0.132) — an in-silico prediction, not a clinical call.

COMMD9 p.Ala57Ser

c.169G>T · VCV4232733

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.132 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00113%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.132	likely benign
REVEL	0.194	benign-leaning
SaProt	LLR -9.17	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 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 15 kb · p 0.55 · regional, not allelic
Overall
CADD	24.1	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00113% South Asian · 1/88,760 alleles

Overall 6.91e-05% 1/1,447,644 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: COMMD9
Protein: p.Ala57Ser
Coding: c.169G>T
MANE Select: NM_014186
Type: single nucleotide variant
Location: chr11:36280720 (GRCh38)
Gene constraint: LOEUF 1.513 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.27 · 7 PDB
Residue 57: an α-helix

Full COMMD9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD9 p.Ala79= Benign ★★ same type
COMMD9 p.Arg110Lys Uncertain significance ★ ⚠ same type
COMMD9 p.Arg122Cys Uncertain significance ★ ⚠ same type
COMMD9 p.Arg141His Uncertain significance ★ ⚠ same type
COMMD9 p.Arg187Cys Uncertain significance ★ ⚠ same type
COMMD9 p.Arg66Cys Uncertain significance ★ ⚠ same type
COMMD9 p.Arg74Cys Uncertain significance ★ ⚠ same type
COMMD9 p.Asp125Asn 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/commd9-p-ala57ser (accessed [today's date]).

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