Is CCDC7 p.Lys2Glu (c.4A>G) pathogenic?

CCDC7 p.Lys2Glu (c.4A>G) is classified Uncertain significance in CCDC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: ambiguous (0.408); Ultra-rare (popmax 0.0476%, eas).

How common is CCDC7 p.Lys2Glu (c.4A>G) in the general population?

CCDC7 p.Lys2Glu (c.4A>G) is ultra-rare (popmax 0.0476%, eas) (gnomAD).

What do computational predictors say about CCDC7 p.Lys2Glu (c.4A>G)?

AlphaMissense predicts ambiguous (score 0.408) — an in-silico prediction, not a clinical call.

CCDC7 p.Lys2Glu

c.4A>G · VCV4221440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.408 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0476%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.408	ambiguous
REVEL	0.162	moderately benign-leaning
SaProt	LLR -6.54	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 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 425 kb · p 0.13 · regional, not allelic
Overall
CADD	20.7	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 0.0476% East Asian · 21/44,094 alleles

Filtering AF 0.0319% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0268%

Overall 0.00184% 29/1,575,404 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0476%	2,100
Remaining individualsnot grpmax-eligible	0.00494%	20,232
European (non-Finnish)	0.00043%	232,440

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.Lys2Glu
Coding: c.4A>G
MANE Select: NM_001395015
Type: single nucleotide variant
Location: chr10:32451646 (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-lys2glu (accessed [today's date]).

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