Is CCDC7 p.Leu8Phe (c.24G>T) pathogenic?

CCDC7 p.Leu8Phe (c.24G>T) is classified Uncertain significance in CCDC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-27). AlphaMissense: likely benign (0.1788); Very rare (popmax 0.00673%, amr).

How common is CCDC7 p.Leu8Phe (c.24G>T) in the general population?

CCDC7 p.Leu8Phe (c.24G>T) is very rare (popmax 0.00673%, amr) (gnomAD).

What do computational predictors say about CCDC7 p.Leu8Phe (c.24G>T)?

AlphaMissense predicts likely benign (score 0.1788) — an in-silico prediction, not a clinical call.

CCDC7 p.Leu8Phe

c.24G>T · rs1357439808 · VCV2303916

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1788 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00673%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1788	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -7.70	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 -0.15	GERP -2.9
Regional constraint	o/e 1.04	unconstrained · MANE · 425 kb · p 0.13 · regional, not allelic
Overall
CADD	9.388	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 0.00673% Admixed American · 4/59,422 alleles

Filtering AF 0.00227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000311% 5/1,608,830 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00673%	14,856
South Asian	0.00111%	89,840

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.Leu8Phe
Coding: c.24G>T
MANE Select: NM_001395015
dbSNP: rs1357439808
Type: single nucleotide variant
Location: chr10:32451666 (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-leu8phe (accessed [today's date]).

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