Is CD2AP p.Arg111His (c.332G>A) pathogenic?

CD2AP p.Arg111His (c.332G>A) is classified Uncertain significance in CD2AP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-12). AlphaMissense: likely benign (0.3107); Ultra-rare (popmax 0.0763%, afr); Associated with focal segmental glomerulosclerosis 3, susceptibility to.

What condition is associated with CD2AP p.Arg111His (c.332G>A)?

CD2AP p.Arg111His (c.332G>A) is associated with focal segmental glomerulosclerosis 3, susceptibility to (ClinVar).

How common is CD2AP p.Arg111His (c.332G>A) in the general population?

CD2AP p.Arg111His (c.332G>A) is ultra-rare (popmax 0.0763%, afr) (gnomAD).

What do computational predictors say about CD2AP p.Arg111His (c.332G>A)?

AlphaMissense predicts likely benign (score 0.3107) — an in-silico prediction, not a clinical call.

CD2AP p.Arg111His

c.332G>A · rs192679464 · VCV2159429

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3107 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0763%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

focal segmental glomerulosclerosis 3, susceptibility to

Computational evidence

Protein change
AlphaMissense	0.3107	likely benign
REVEL	0.378	indeterminate
SaProt	LLR -11.07	damaging
⇒ SaProt calls this damaging; AlphaMissense 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	34.0	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 0.0763% African / African-American · 57/74,698 alleles

Filtering AF 0.0604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0547%

Overall 0.00773% 124/1,604,914 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0763%	1,310
European (non-Finnish)	0.0052%	19,215
Remaining individualsnot grpmax-eligible	0.00483%	20,719
East Asian	0.00224%	44,730
Admixed American	0.00167%	59,962
South Asian	0.0011%	90,890

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.Arg111His
Coding: c.332G>A
MANE Select: NM_012120
dbSNP: rs192679464
Type: single nucleotide variant
Location: chr6:47544618 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 111: the sh3 2 domain; 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

focal segmental glomerulosclerosis 3, susceptibility to — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD2AP p.Arg111fs Likely pathogenic ★ same residue
CD2AP p.Arg111Cys Uncertain significance ★ ⚠ same residue
CD2AP c.1274+3A>G Uncertain significance ★★ same condition
CD2AP c.1633-6T>A Uncertain significance ★★ same condition
CD2AP c.-130C>G Uncertain significance ★★ same condition
CD2AP c.-166A>G Uncertain significance ★★ same condition
CD2AP c.*319A>C Uncertain significance ★★ same condition
CD2AP c.*452C>G 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-arg111his (accessed [today's date]).

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