Is CD2AP p.Val54Ile (c.160G>A) pathogenic?

CD2AP p.Val54Ile (c.160G>A) is classified Uncertain significance in CD2AP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-04-29). AlphaMissense: ambiguous (0.3785); Ultra-rare (popmax 0.0179%, eas); Associated with Inborn genetic diseases.

What condition is associated with CD2AP p.Val54Ile (c.160G>A)?

CD2AP p.Val54Ile (c.160G>A) is associated with Inborn genetic diseases, focal segmental glomerulosclerosis 3, susceptibility to (ClinVar).

How common is CD2AP p.Val54Ile (c.160G>A) in the general population?

CD2AP p.Val54Ile (c.160G>A) is ultra-rare (popmax 0.0179%, eas) (gnomAD).

What do computational predictors say about CD2AP p.Val54Ile (c.160G>A)?

AlphaMissense predicts ambiguous (score 0.3785) — an in-silico prediction, not a clinical call.

CD2AP p.Val54Ile

c.160G>A · rs764144193 · VCV1947012

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3785 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3785	ambiguous
REVEL	0.284	benign-leaning
SaProt	LLR -10.96	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense 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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0179% East Asian · 8/44,812 alleles

Filtering AF 0.00885% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00642%

Overall 0.00118% 19/1,613,142 alleles · ultra-rare exomes 16/1,460,982 · genomes 3/152,160 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0179%	5,601
Admixed American	0.005%	19,998
Remaining individualsnot grpmax-eligible	0.0032%	31,225
South Asian	0.0022%	45,531
European (non-Finnish)	0.000339%	294,832

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.Val54Ile
Coding: c.160G>A
MANE Select: NM_012120
dbSNP: rs764144193
Type: single nucleotide variant
Location: chr6:47503435 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 54: 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

Disease context

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

Also linked: focal segmental glomerulosclerosis 3, susceptibility to

Similar variants

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
CD2AP c.*494G>A Uncertain significance ★★ same condition
CD2AP c.*496A>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-val54ile (accessed [today's date]).

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