Is CCDC7 p.Glu149Asp (c.447A>C) pathogenic?

CCDC7 p.Glu149Asp (c.447A>C) is classified Uncertain significance in CCDC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-15). AlphaMissense: ambiguous (0.5037); Very rare (popmax 0.00506%, amr).

How common is CCDC7 p.Glu149Asp (c.447A>C) in the general population?

CCDC7 p.Glu149Asp (c.447A>C) is very rare (popmax 0.00506%, amr) (gnomAD).

What do computational predictors say about CCDC7 p.Glu149Asp (c.447A>C)?

AlphaMissense predicts ambiguous (score 0.5037) — an in-silico prediction, not a clinical call.

CCDC7 p.Glu149Asp

c.447A>C · VCV3264271

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5037 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00506%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5037	ambiguous · top 8% in CCDC7
REVEL	0.182	moderately benign-leaning
SaProt	LLR -7.27	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.007, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 425 kb · p 0.13 · regional, not allelic
Overall
CADD	16.11	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00506% Admixed American · 3/59,332 alleles

Filtering AF 0.00134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000672%

Overall 0.00102% 16/1,571,438 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00506%	19,777
African / African-American	0.00268%	37,249
European (non-Finnish)	0.000956%	104,590

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: CCDC7
Protein: p.Glu149Asp
Coding: c.447A>C
MANE Select: NM_001395015
Type: single nucleotide variant
Location: chr10:32456325 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.53

Full CCDC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC7 c.3604+1G>C Uncertain significance ★ same type
CCDC7 p.Ala381Val Uncertain significance ★ ⚠ same type
CCDC7 p.Arg209Cys Uncertain significance ★ ⚠ same type
CCDC7 p.Arg274Gln Uncertain significance ★ ⚠ same type
CCDC7 p.Arg855Cys Uncertain significance ★ ⚠ same type
CCDC7 p.Asn12Ser Uncertain significance ★ ⚠ same type
CCDC7 p.Asn192Asp Uncertain significance ★ ⚠ same type
CCDC7 p.Asp1266Tyr 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/ccdc7-p-glu149asp (accessed [today's date]).

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