Is CCDC7 p.Ser96Pro (c.286T>C) pathogenic?

CCDC7 p.Ser96Pro (c.286T>C) is classified Uncertain significance in CCDC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely pathogenic (0.7401); Very rare (popmax 0.000267%, nfe).

How common is CCDC7 p.Ser96Pro (c.286T>C) in the general population?

CCDC7 p.Ser96Pro (c.286T>C) is very rare (popmax 0.000267%, nfe) (gnomAD).

What do computational predictors say about CCDC7 p.Ser96Pro (c.286T>C)?

AlphaMissense predicts likely pathogenic (score 0.7401) — an in-silico prediction, not a clinical call.

CCDC7 p.Ser96Pro

c.286T>C · VCV4649627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7401 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000267%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7401	likely pathogenic · top 3% in CCDC7
REVEL	0.274	benign-leaning
SaProt	LLR -10.10	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.51	GERP -0.98, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 425 kb · p 0.13 · regional, not allelic
Overall
CADD	17.32	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 0.000267% European (non-Finnish) · 3/1,125,052 alleles

Filtering AF 7.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.0002% 3/1,497,120 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: CCDC7
Protein: p.Ser96Pro
Coding: c.286T>C
MANE Select: NM_001395015
Type: single nucleotide variant
Location: chr10:32453350 (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-ser96pro (accessed [today's date]).

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