Is CD2AP p.His14= (c.42T>C) pathogenic?

CD2AP p.His14= (c.42T>C) is classified Benign/Likely benign in CD2AP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-10). Low-frequency (popmax 1.59%, afr); Associated with focal segmental glomerulosclerosis 3, susceptibility to.

What condition is associated with CD2AP p.His14= (c.42T>C)?

CD2AP p.His14= (c.42T>C) is associated with focal segmental glomerulosclerosis 3, susceptibility to (ClinVar).

How common is CD2AP p.His14= (c.42T>C) in the general population?

CD2AP p.His14= (c.42T>C) is low-frequency (popmax 1.59%, afr) (gnomAD).

CD2AP p.His14=

c.42T>C · rs34773184 · VCV792040

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.59%, afr)

Conditions

focal segmental glomerulosclerosis 3, susceptibility to

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 0.89	GERP -2.6, phastCons 1
Overall
CADD	8.035	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.59% African / African-American · 1,194/75,008 alleles

Filtering AF 1.52% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.49%

Overall 0.0855% 1,380/1,613,834 alleles · low-frequency exomes 705/1,461,554 · genomes 675/152,280 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.59%	63
Admixed American	0.122%	822
Remaining individualsnot grpmax-eligible	0.117%	856
Middle Eastern	0.099%	1,010
South Asian	0.0121%	8,280
European (non-Finnish)	0.00195%	51,297

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.His14=
Coding: c.42T>C
MANE Select: NM_012120
dbSNP: rs34773184
Type: single nucleotide variant
Location: chr6:47503317 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 12 PDB
Residue 14: the sh3 1; truncated 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 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-his14 (accessed [today's date]).

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