Is CCDC47 p.Asp229Val (c.686A>T) pathogenic?

CCDC47 p.Asp229Val (c.686A>T) is classified Uncertain significance in CCDC47 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely pathogenic (0.9972); Very rare (popmax 8.48e-05%, nfe).

How common is CCDC47 p.Asp229Val (c.686A>T) in the general population?

CCDC47 p.Asp229Val (c.686A>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CCDC47 p.Asp229Val (c.686A>T)?

AlphaMissense predicts likely pathogenic (score 0.9972) — an in-silico prediction, not a clinical call.

CCDC47 p.Asp229Val

c.686A>T · VCV3828651

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9972 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9972	likely pathogenic · top 6% in CCDC47
REVEL	0.856	moderately pathogenic-leaning
SaProt	LLR -11.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 5.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 19 kb · p 0.0049 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.48e-05% European (non-Finnish) · 1/1,179,650 alleles

Overall 6.84e-05% 1/1,461,478 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: CCDC47
Protein: p.Asp229Val
Coding: c.686A>T
MANE Select: NM_020198
Type: single nucleotide variant
Location: chr17:63760963 (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-asp229val (accessed [today's date]).

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