Is CCDC47 p.Tyr293Phe (c.878A>T) pathogenic?

CCDC47 p.Tyr293Phe (c.878A>T) is classified Uncertain significance in CCDC47 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). AlphaMissense: likely benign (0.0657); Very rare (popmax 0.00133%, afr).

How common is CCDC47 p.Tyr293Phe (c.878A>T) in the general population?

CCDC47 p.Tyr293Phe (c.878A>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CCDC47 p.Tyr293Phe (c.878A>T)?

AlphaMissense predicts likely benign (score 0.0657) — an in-silico prediction, not a clinical call.

CCDC47 p.Tyr293Phe

c.878A>T · VCV3486732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0657 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0657	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -7.71	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 7.8	GERP 5.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 19 kb · p 0.0049 · regional, not allelic
Overall
CADD	19.68	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 0.00133% African / African-American · 1/74,940 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000682% 11/1,614,080 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-Americangrpmax	0.00133%	74,940
European (non-Finnish)	0.000763%	131,114

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Tyr293Phe
Coding: c.878A>T
MANE Select: NM_020198
Type: single nucleotide variant
Location: chr17:63756310 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.07 · 1 PDB
Residue 293: a UniProt-annotated variant site (in thns; loss-of-function variant affecting er calcium ion homeostasis in patient cells; no protein detected by western blot in patient cells)

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-tyr293phe (accessed [today's date]).

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