Is CCDC47 p.Phe25Ser (c.74T>C) pathogenic?

CCDC47 p.Phe25Ser (c.74T>C) is classified Uncertain significance in CCDC47 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely benign (0.2625); Ultra-rare (popmax 0.0713%, eas).

How common is CCDC47 p.Phe25Ser (c.74T>C) in the general population?

CCDC47 p.Phe25Ser (c.74T>C) is ultra-rare (popmax 0.0713%, eas) (gnomAD).

What do computational predictors say about CCDC47 p.Phe25Ser (c.74T>C)?

AlphaMissense predicts likely benign (score 0.2625) — an in-silico prediction, not a clinical call.

CCDC47 p.Phe25Ser

c.74T>C · rs376932310 · VCV3139176

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2625 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0713%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2625	likely benign
REVEL	0.262	benign-leaning
SaProt	LLR -9.96	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 11	GERP 5.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 19 kb · p 0.0049 · regional, not allelic
Overall
CADD	25.2	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 0.0713% East Asian · 32/44,882 alleles

Filtering AF 0.0519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0452%

Overall 0.00198% 32/1,613,948 alleles · ultra-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: CCDC47
Protein: p.Phe25Ser
Coding: c.74T>C
MANE Select: NM_020198
dbSNP: rs376932310
Type: single nucleotide variant
Location: chr17:63766102 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.07 · 1 PDB

Full CCDC47 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC47 p.Arg397Ter Pathogenic/Likely pathogenic ★★ same type
CCDC47 p.Asp75Tyr Uncertain significance ★★ ⚠ same type
CCDC47 p.Trp133Arg Uncertain significance ★★ ⚠ same type
CCDC47 c.1093+112G>A Benign ★★ same type
CCDC47 c.1094-3C>T Benign ★★ same type
CCDC47 c.735+15C>T Benign ★★ same type
CCDC47 p.Arg271Ter Likely pathogenic ★ same type
CCDC47 c.669+5G>T 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/ccdc47-p-phe25ser (accessed [today's date]).

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