Is CCDC167 p.Val91Ala (c.272T>C) pathogenic?

CCDC167 p.Val91Ala (c.272T>C) is classified Uncertain significance in CCDC167 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-29). AlphaMissense: likely benign (0.1176); Ultra-rare (popmax 0.0879%, afr).

How common is CCDC167 p.Val91Ala (c.272T>C) in the general population?

CCDC167 p.Val91Ala (c.272T>C) is ultra-rare (popmax 0.0879%, afr) (gnomAD).

What do computational predictors say about CCDC167 p.Val91Ala (c.272T>C)?

AlphaMissense predicts likely benign (score 0.1176) — an in-silico prediction, not a clinical call.

CCDC167 p.Val91Ala

c.272T>C · rs146517218 · VCV2344053

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1176 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0879%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1176	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -5.92	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 6.1	GERP 1.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 17 kb · p 0.94 · regional, not allelic
Overall
CADD	20.2	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 0.0879% African / African-American · 66/75,064 alleles

Filtering AF 0.0709% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0647%

Overall 0.00446% 72/1,614,020 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0879%	1,137
Admixed American	0.00666%	15,006
Remaining individualsnot grpmax-eligible	0.0032%	31,249

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: CCDC167
Protein: p.Val91Ala
Coding: c.272T>C
MANE Select: NM_138493
dbSNP: rs146517218
Type: single nucleotide variant
Location: chr6:37483208 (GRCh38)
Gene constraint: LOEUF 1.702 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71

Full CCDC167 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC167 p.Val91Ile Likely benign ★ same residue
CCDC167 p.Ala60Ser Uncertain significance ★ ⚠ same type
CCDC167 p.Arg26Gln Uncertain significance ★ ⚠ same type
CCDC167 p.Arg26Trp Uncertain significance ★ ⚠ same type
CCDC167 p.Arg35Gly Uncertain significance ★ ⚠ same type
CCDC167 p.Arg39Trp Uncertain significance ★ ⚠ same type
CCDC167 p.Arg75Gln Uncertain significance ★ ⚠ same type
CCDC167 p.Asn77Ser 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/ccdc167-p-val91ala (accessed [today's date]).

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