Is COMMD7 p.Ser145Phe (c.434C>T) pathogenic?

COMMD7 p.Ser145Phe (c.434C>T) is classified Uncertain significance in COMMD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-28). AlphaMissense: likely pathogenic (0.6448); Very rare (popmax 0.00225%, eas).

How common is COMMD7 p.Ser145Phe (c.434C>T) in the general population?

COMMD7 p.Ser145Phe (c.434C>T) is very rare (popmax 0.00225%, eas) (gnomAD).

What do computational predictors say about COMMD7 p.Ser145Phe (c.434C>T)?

AlphaMissense predicts likely pathogenic (score 0.6448) — an in-silico prediction, not a clinical call.

COMMD7 p.Ser145Phe

c.434C>T · VCV3268927

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6448 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00225%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6448	likely pathogenic
REVEL	0.082	moderately benign-leaning
SaProt	LLR -10.48	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 40 kb · p 0.049 · regional, not allelic
Overall
CADD	29.6	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 0.00225% East Asian · 1/44,490 alleles

Overall 0.000766% 1/130,558 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: COMMD7
Protein: p.Ser145Phe
Coding: c.434C>T
MANE Select: NM_053041
Type: single nucleotide variant
Location: chr20:32704483 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.76 · 4 PDB
Residue 145: the comm domain; a β-strand

Full COMMD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD7 c.526+3G>A Benign ★★ same type
COMMD7 p.Ala117Val Uncertain significance ★ ⚠ same type
COMMD7 p.Ala121Val Uncertain significance ★ ⚠ same type
COMMD7 p.Ala14Ser Uncertain significance ★ ⚠ same type
COMMD7 p.Ala32Asp Uncertain significance ★ ⚠ same type
COMMD7 p.Ala94Val Uncertain significance ★ ⚠ same type
COMMD7 p.Arg122Gly Uncertain significance ★ ⚠ same type
COMMD7 p.Asn168Ser 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/commd7-p-ser145phe (accessed [today's date]).

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