Is COMMD5 p.Phe54Leu (c.160T>C) pathogenic?

COMMD5 p.Phe54Leu (c.160T>C) is classified Likely benign in COMMD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-28). AlphaMissense: likely benign (0.1499); Very rare (popmax 0.00533%, afr).

How common is COMMD5 p.Phe54Leu (c.160T>C) in the general population?

COMMD5 p.Phe54Leu (c.160T>C) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about COMMD5 p.Phe54Leu (c.160T>C)?

AlphaMissense predicts likely benign (score 0.1499) — an in-silico prediction, not a clinical call.

COMMD5 p.Phe54Leu

c.160T>C · VCV4655797

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1499 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1499	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -2.59	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 4.2	GERP -0.73, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 671 bp · p 0.0015 · regional, not allelic
Overall
CADD	14.31	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 0.00533% African / African-American · 4/74,982 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000479% 7/1,461,400 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,746
Remaining individualsnot grpmax-eligible	0.0032%	31,251
South Asian	0.0011%	91,060

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: COMMD5
Protein: p.Phe54Leu
Coding: c.160T>C
MANE Select: NM_014066
Type: single nucleotide variant
Location: chr8:144851179 (GRCh38)
Gene constraint: LOEUF 1.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.49 · 4 PDB
Residue 54: an α-helix

Full COMMD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD5 p.Ala153Thr Uncertain significance ★ ⚠ same type
COMMD5 p.Arg135Gln Uncertain significance ★ ⚠ same type
COMMD5 p.Arg158Trp Uncertain significance ★ ⚠ same type
COMMD5 p.Arg201Gln Uncertain significance ★ ⚠ same type
COMMD5 p.Arg217Ser Uncertain significance ★ ⚠ same type
COMMD5 p.Arg220His Uncertain significance ★ ⚠ same type
COMMD5 p.Arg65Gln Uncertain significance ★ ⚠ same type
COMMD5 p.Arg70His 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/commd5-p-phe54leu (accessed [today's date]).

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