Is CCDC74B p.Val243Phe (c.727G>T) pathogenic?

CCDC74B p.Val243Phe (c.727G>T) is classified Uncertain significance in CCDC74B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). AlphaMissense: likely benign (0.1041); Absent from gnomAD v4.1.

How common is CCDC74B p.Val243Phe (c.727G>T) in the general population?

CCDC74B p.Val243Phe (c.727G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC74B p.Val243Phe (c.727G>T)?

AlphaMissense predicts likely benign (score 0.1041) — an in-silico prediction, not a clinical call.

CCDC74B p.Val243Phe

c.727G>T · VCV3828784

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1041 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1041	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -7.65	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 -0.27
Regional constraint	o/e 1.00	unconstrained · MANE · 1,637 bp · p 0.96 · regional, not allelic
Overall
CADD	8.014	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V309F vs ClinVar V243F) — verify the residue.

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: CCDC74B
Protein: p.Val243Phe
Coding: c.727G>T
MANE Select: NM_001258307
Type: single nucleotide variant
Location: chr2:130140048 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.67

Full CCDC74B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC74B c.296-114C>T Uncertain significance ★ ⚠ same type
CCDC74B c.296-115C>G Uncertain significance ★ ⚠ same type
CCDC74B c.296-117A>C Uncertain significance ★ ⚠ same type
CCDC74B c.296-129G>C Uncertain significance ★ ⚠ same type
CCDC74B c.296-131C>A Uncertain significance ★ ⚠ same type
CCDC74B c.296-13C>T Uncertain significance ★ ⚠ same type
CCDC74B c.296-147G>A Uncertain significance ★ ⚠ same type
CCDC74B c.296-148C>A 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/ccdc74b-p-val243phe (accessed [today's date]).

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