Is CCDC191 p.Pro515Ala (c.1543C>G) pathogenic?

CCDC191 p.Pro515Ala (c.1543C>G) is classified Uncertain significance in CCDC191 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-27). AlphaMissense: likely benign (0.059); Absent from gnomAD v4.1.

How common is CCDC191 p.Pro515Ala (c.1543C>G) in the general population?

CCDC191 p.Pro515Ala (c.1543C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC191 p.Pro515Ala (c.1543C>G)?

AlphaMissense predicts likely benign (score 0.059) — an in-silico prediction, not a clinical call.

CCDC191 p.Pro515Ala

c.1543C>G · VCV3486581

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.059 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.059	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -5.91	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 0.88	GERP -4.5, phastCons 0.011
Regional constraint	o/e 0.90	unconstrained · MANE · 91 kb · p 0.00055 · regional, not allelic
Overall
CADD	0.92	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCDC191
Protein: p.Pro515Ala
Coding: c.1543C>G
MANE Select: NM_020817
Type: single nucleotide variant
Location: chr3:114005833 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.36
Residue 515: the 'disordered' region

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-pro515ala (accessed [today's date]).

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