Is CD2AP p.Glu305Lys (c.913G>A) pathogenic?

CD2AP p.Glu305Lys (c.913G>A) is classified Uncertain significance in CD2AP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-09). AlphaMissense: likely pathogenic (0.6771); Very rare (popmax 0.00446%, eas).

How common is CD2AP p.Glu305Lys (c.913G>A) in the general population?

CD2AP p.Glu305Lys (c.913G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CD2AP p.Glu305Lys (c.913G>A)?

AlphaMissense predicts likely pathogenic (score 0.6771) — an in-silico prediction, not a clinical call.

CD2AP p.Glu305Lys

c.913G>A · rs1375273345 · VCV1904241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6771 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6771	likely pathogenic
REVEL	0.37	indeterminate
SaProt	LLR -13.95	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 146 kb · p 0.14 · regional, not allelic
Overall
CADD	29.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00446% East Asian · 2/44,800 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000249% 4/1,603,334 alleles · very rare exomes 3/1,451,408 · genomes 1/151,926 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,400
Remaining individualsnot grpmax-eligible	0.00161%	62,132
South Asian	0.0011%	90,880

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: CD2AP
Protein: p.Glu305Lys
Coding: c.913G>A
MANE Select: NM_012120
dbSNP: rs1375273345
Type: single nucleotide variant
Location: chr6:47579394 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 305: the sh3 3 domain

Full CD2AP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD2AP c.1274+3A>G Uncertain significance ★★ same type
CD2AP c.1633-6T>A Uncertain significance ★★ same type
CD2AP c.-130C>G Uncertain significance ★★ same type
CD2AP c.-166A>G Uncertain significance ★★ same type
CD2AP c.*319A>C Uncertain significance ★★ same type
CD2AP c.*452C>G Uncertain significance ★★ same type
CD2AP c.*494G>A Uncertain significance ★★ same type
CD2AP c.*496A>G 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/cd2ap-p-glu305lys (accessed [today's date]).

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