Is CD2AP p.Arg84Gln (c.251G>A) pathogenic?

CD2AP p.Arg84Gln (c.251G>A) is classified Uncertain significance in CD2AP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-18). AlphaMissense: likely pathogenic (0.5925); Ultra-rare (popmax 0.0467%, afr); Associated with Inborn genetic diseases.

What condition is associated with CD2AP p.Arg84Gln (c.251G>A)?

CD2AP p.Arg84Gln (c.251G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CD2AP p.Arg84Gln (c.251G>A) in the general population?

CD2AP p.Arg84Gln (c.251G>A) is ultra-rare (popmax 0.0467%, afr) (gnomAD).

What do computational predictors say about CD2AP p.Arg84Gln (c.251G>A)?

AlphaMissense predicts likely pathogenic (score 0.5925) — an in-silico prediction, not a clinical call.

CD2AP p.Arg84Gln

c.251G>A · rs371293071 · VCV2360329

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5925 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0467%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5925	likely pathogenic
REVEL	0.318	indeterminate
SaProt	LLR -5.74	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 146 kb · p 0.14 · regional, not allelic
Overall
CADD	33.0	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 0.0467% African / African-American · 35/74,896 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0303%

Overall 0.00378% 61/1,613,922 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0467%	2,140
South Asian	0.0187%	5,358
Remaining individualsnot grpmax-eligible	0.0048%	20,828
Admixed American	0.00333%	29,999
European (non-Finnish)	0.000339%	294,996

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.Arg84Gln
Coding: c.251G>A
MANE Select: NM_012120
dbSNP: rs371293071
Type: single nucleotide variant
Location: chr6:47533687 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 84: the 'interaction with anln and localization to the midbody' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD2AP p.Arg84Ter Likely pathogenic ★ same residue
CD2AP p.Arg228Gln Uncertain significance ★★ ⚠ same condition
CD2AP p.Arg504Cys Uncertain significance ★★ same condition
CD2AP p.Asn427Ser Uncertain significance ★★ ⚠ same condition
CD2AP p.Asn506Ser Uncertain significance ★★ ⚠ same condition
CD2AP p.Asp473Gly Uncertain significance ★★ ⚠ same condition
CD2AP p.Gly605Arg Uncertain significance ★★ ⚠ same condition
CD2AP p.His174Pro Uncertain significance ★★ ⚠ same condition

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-arg84gln (accessed [today's date]).

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