Is CD2AP p.Arg27Ser (c.81G>T) pathogenic?

CD2AP p.Arg27Ser (c.81G>T) is classified Uncertain significance in CD2AP (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-19). AlphaMissense: likely pathogenic (0.5902); Absent from gnomAD v4.1.

How common is CD2AP p.Arg27Ser (c.81G>T) in the general population?

CD2AP p.Arg27Ser (c.81G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD2AP p.Arg27Ser (c.81G>T)?

AlphaMissense predicts likely pathogenic (score 0.5902) — an in-silico prediction, not a clinical call.

CD2AP p.Arg27Ser

c.81G>T · rs1283834941 · VCV1040301

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5902 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5902	likely pathogenic
REVEL	0.272	benign-leaning
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -1.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 146 kb · p 0.14 · regional, not allelic
Overall
CADD	24.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD2AP
Protein: p.Arg27Ser
Coding: c.81G>T
MANE Select: NM_012120
dbSNP: rs1283834941
Type: single nucleotide variant
Location: chr6:47503356 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 27: the sh3 1; truncated domain; a β-strand; the 'interaction with anln and localization to the midbody' region

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-arg27ser (accessed [today's date]).

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