Is COMMD6 p.Phe61Ser (c.182T>C) pathogenic?

COMMD6 p.Phe61Ser (c.182T>C) is classified Uncertain significance in COMMD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely pathogenic (0.9431); Absent from gnomAD v4.1.

How common is COMMD6 p.Phe61Ser (c.182T>C) in the general population?

COMMD6 p.Phe61Ser (c.182T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COMMD6 p.Phe61Ser (c.182T>C)?

AlphaMissense predicts likely pathogenic (score 0.9431) — an in-silico prediction, not a clinical call.

COMMD6 p.Phe61Ser

c.182T>C · VCV3495903

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9431 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9431	likely pathogenic
REVEL	0.592	indeterminate
SaProt	LLR -14.15	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 11 kb · p 0.033 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COMMD6
Protein: p.Phe61Ser
Coding: c.182T>C
MANE Select: NM_203495
Type: single nucleotide variant
Location: chr13:75530139 (GRCh38)
Gene constraint: LOEUF 1.538 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 85.37 · 3 PDB
Residue 61: the comm domain; a β-strand

Full COMMD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD6 p.Ala50Pro Uncertain significance ★ ⚠ same type
COMMD6 p.Asp33Asn Uncertain significance ★ ⚠ same type
COMMD6 p.Ile82Thr Uncertain significance ★ ⚠ same type
COMMD6 p.Lys57Asn Uncertain significance ★ ⚠ same type
COMMD6 p.Met28Val Uncertain significance ★ ⚠ same type
COMMD6 p.Met46Ile Uncertain significance ★ ⚠ same type
COMMD6 p.Val30Met 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/commd6-p-phe61ser (accessed [today's date]).

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