Is CCDC191 p.Val912Ile (c.2734G>A) pathogenic?

CCDC191 p.Val912Ile (c.2734G>A) is classified Uncertain significance in CCDC191 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely benign (0.0984); Very rare (popmax 0.00221%, sas).

How common is CCDC191 p.Val912Ile (c.2734G>A) in the general population?

CCDC191 p.Val912Ile (c.2734G>A) is very rare (popmax 0.00221%, sas) (gnomAD).

What do computational predictors say about CCDC191 p.Val912Ile (c.2734G>A)?

AlphaMissense predicts likely benign (score 0.0984) — an in-silico prediction, not a clinical call.

CCDC191 p.Val912Ile

c.2734G>A · rs1207773359 · VCV2496023

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0984 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00221%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0984	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.30	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -1.5	GERP -3.1
Regional constraint	o/e 0.90	unconstrained · MANE · 91 kb · p 0.00055 · regional, not allelic
Overall
CADD	0.008	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 0.00221% South Asian · 2/90,630 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000744% 12/1,612,122 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00221%	45,315
European (non-Finnish)	0.000848%	117,923

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: CCDC191
Protein: p.Val912Ile
Coding: c.2734G>A
MANE Select: NM_020817
dbSNP: rs1207773359
Type: single nucleotide variant
Location: chr3:113965232 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.36

Full CCDC191 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC191 p.Ala331Thr Uncertain significance ★ ⚠ same type
CCDC191 p.Ala347Thr Uncertain significance ★ ⚠ same type
CCDC191 p.Ala415Thr Uncertain significance ★ ⚠ same type
CCDC191 p.Ala596Ser Uncertain significance ★ ⚠ same type
CCDC191 p.Ala669Val Uncertain significance ★ ⚠ same type
CCDC191 p.Ala800Asp Uncertain significance ★ ⚠ same type
CCDC191 p.Ala800Val Uncertain significance ★ ⚠ same type
CCDC191 p.Arg19Leu 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/ccdc191-p-val912ile (accessed [today's date]).

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