Is CCDC175 p.Val304Ala (c.911T>C) pathogenic?

CCDC175 p.Val304Ala (c.911T>C) is classified Uncertain significance in CCDC175 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-30). AlphaMissense: likely benign (0.2739); Very rare (popmax 0.00157%, nfe).

How common is CCDC175 p.Val304Ala (c.911T>C) in the general population?

CCDC175 p.Val304Ala (c.911T>C) is very rare (popmax 0.00157%, nfe) (gnomAD).

What do computational predictors say about CCDC175 p.Val304Ala (c.911T>C)?

AlphaMissense predicts likely benign (score 0.2739) — an in-silico prediction, not a clinical call.

CCDC175 p.Val304Ala

c.911T>C · VCV3264097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2739 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00157%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2739	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -7.23	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 5.1	GERP 1.3, phastCons 0.36
Regional constraint	o/e 0.96	unconstrained · MANE · 72 kb · p 0.21 · regional, not allelic
Overall
CADD	16.82	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 0.00157% European (non-Finnish) · 18/1,145,622 alleles

Filtering AF 0.000982% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00081%

Overall 0.00117% 18/1,535,402 alleles · very rare

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: CCDC175
Protein: p.Val304Ala
Coding: c.911T>C
MANE Select: NM_001164399
Type: single nucleotide variant
Location: chr14:59561161 (GRCh38)
Gene constraint: LOEUF 1.235 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.01

Full CCDC175 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC175 p.Ala124Thr Uncertain significance ★ ⚠ same type
CCDC175 p.Ala219Val Uncertain significance ★ ⚠ same type
CCDC175 p.Ala228Pro Uncertain significance ★ ⚠ same type
CCDC175 p.Ala316Val Uncertain significance ★ ⚠ same type
CCDC175 p.Ala353Pro Uncertain significance ★ ⚠ same type
CCDC175 p.Ala429Ser Uncertain significance ★ ⚠ same type
CCDC175 p.Arg122Gln Uncertain significance ★ ⚠ same type
CCDC175 p.Arg206Gly 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/ccdc175-p-val304ala (accessed [today's date]).

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