Is CCDC91 p.Val129Ala (c.386T>C) pathogenic?

CCDC91 p.Val129Ala (c.386T>C) is classified Uncertain significance in CCDC91 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-14). AlphaMissense: likely benign (0.1043); Ultra-rare (popmax 0.0134%, eas).

How common is CCDC91 p.Val129Ala (c.386T>C) in the general population?

CCDC91 p.Val129Ala (c.386T>C) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about CCDC91 p.Val129Ala (c.386T>C)?

AlphaMissense predicts likely benign (score 0.1043) — an in-silico prediction, not a clinical call.

CCDC91 p.Val129Ala

c.386T>C · VCV4649836

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1043 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1043	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.84	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 0.53	GERP 0.61
Regional constraint	o/e 1.01	unconstrained · MANE · 292 kb · p 0.81 · regional, not allelic
Overall
CADD	14.07	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 0.0134% East Asian · 6/44,764 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00395%

Overall 0.000616% 9/1,460,108 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,461
European (non-Finnish)	0.000255%	392,896

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: CCDC91
Protein: p.Val129Ala
Coding: c.386T>C
MANE Select: NM_018318
Type: single nucleotide variant
Location: chr12:28306860 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 76.04 · 1 PDB

Full CCDC91 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC91 p.Asp121Gly Benign ★★ same type
CCDC91 p.Gln403Lys Benign ★★ ⚠ same type
CCDC91 p.Ala127Thr Uncertain significance ★ ⚠ same type
CCDC91 p.Ala181Thr Uncertain significance ★ ⚠ same type
CCDC91 p.Ala209Thr Uncertain significance ★ ⚠ same type
CCDC91 p.Ala219Thr Uncertain significance ★ ⚠ same type
CCDC91 p.Ala28Ser Uncertain significance ★ ⚠ same type
CCDC91 p.Ala334Gly 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/ccdc91-p-val129ala (accessed [today's date]).

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