Is CD2AP p.Ala279= (c.837C>T) pathogenic?

CD2AP p.Ala279= (c.837C>T) is classified Likely benign in CD2AP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Very rare (popmax 0.00275%, nfe).

How common is CD2AP p.Ala279= (c.837C>T) in the general population?

CD2AP p.Ala279= (c.837C>T) is very rare (popmax 0.00275%, nfe) (gnomAD).

CD2AP p.Ala279=

c.837C>T · rs765258692 · VCV1544401

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00275%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP -4, phastCons 0.46
Overall
CADD	5.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00275% European (non-Finnish) · 30/1,092,730 alleles

Filtering AF 0.00195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00169%

Overall 0.00217% 33/1,517,746 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00275%	36,424
Remaining individualsnot grpmax-eligible	0.00169%	59,196
Admixed American	0.00167%	59,852
African / African-American	0.00137%	73,028

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.Ala279=
Coding: c.837C>T
MANE Select: NM_012120
dbSNP: rs765258692
Type: single nucleotide variant
Location: chr6:47577037 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 279: 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-ala279 (accessed [today's date]).

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