Is CCDC191 p.Arg877Gln (c.2630G>A) pathogenic?

CCDC191 p.Arg877Gln (c.2630G>A) is classified Likely benign in CCDC191 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely benign (0.0589); Very rare (popmax 0.00392%, nfe).

How common is CCDC191 p.Arg877Gln (c.2630G>A) in the general population?

CCDC191 p.Arg877Gln (c.2630G>A) is very rare (popmax 0.00392%, nfe) (gnomAD).

What do computational predictors say about CCDC191 p.Arg877Gln (c.2630G>A)?

AlphaMissense predicts likely benign (score 0.0589) — an in-silico prediction, not a clinical call.

CCDC191 p.Arg877Gln

c.2630G>A · VCV4649415

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0589 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00392%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0589	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -5.56	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 0.65	GERP -2.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 91 kb · p 0.00055 · regional, not allelic
Overall
CADD	15.08	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 0.00392% European (non-Finnish) · 46/1,172,412 alleles

Filtering AF 0.00301% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00269%

Overall 0.00313% 50/1,596,572 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00392%	25,487
South Asian	0.00228%	43,767
Admixed American	0.00175%	57,234
African / African-American	0.00135%	73,900

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.Arg877Gln
Coding: c.2630G>A
MANE Select: NM_020817
Type: single nucleotide variant
Location: chr3:113965336 (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-arg877gln (accessed [today's date]).

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