Is CCDC7 p.His90Arg (c.269A>G) pathogenic?

CCDC7 p.His90Arg (c.269A>G) is classified Uncertain significance in CCDC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-17). AlphaMissense: likely benign (0.3293); Very rare (popmax 0.00775%, sas).

How common is CCDC7 p.His90Arg (c.269A>G) in the general population?

CCDC7 p.His90Arg (c.269A>G) is very rare (popmax 0.00775%, sas) (gnomAD).

What do computational predictors say about CCDC7 p.His90Arg (c.269A>G)?

AlphaMissense predicts likely benign (score 0.3293) — an in-silico prediction, not a clinical call.

CCDC7 p.His90Arg

c.269A>G · VCV3828743

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3293 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00775%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3293	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -4.57	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 3.2	GERP 0.38, phastCons 0.95
Regional constraint	o/e 1.04	unconstrained · MANE · 425 kb · p 0.13 · regional, not allelic
Overall
CADD	11.41	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 0.00775% South Asian · 7/90,370 alleles

Filtering AF 0.00361% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00256%

Overall 0.000617% 9/1,458,738 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00775%	12,910
African / African-American	0.00134%	74,854
European (non-Finnish)	8.48e-05%	1,178,620

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.His90Arg
Coding: c.269A>G
MANE Select: NM_001395015
Type: single nucleotide variant
Location: chr10:32451911 (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-his90arg (accessed [today's date]).

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