Is SRCAP p.Leu1090fs (c.3269del) pathogenic?

SRCAP p.Leu1090fs (c.3269del) is classified Likely pathogenic in SRCAP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-04-26). Very rare (popmax 8.49e-05%, nfe).

How common is SRCAP p.Leu1090fs (c.3269del) in the general population?

SRCAP p.Leu1090fs (c.3269del) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

SRCAP p.Leu1090fs

c.3269del · rs2506665187 · VCV2577940

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 21 of 34
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.088	GERP -3.4, phastCons 0.001

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,874 alleles

Overall 6.21e-05% 1/1,610,226 alleles · very rare exomes 1/1,457,966 · genomes 0/152,260 · joint denominator

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: SRCAP
Protein: p.Leu1090fs
Coding: c.3269del
MANE Select: NM_006662
dbSNP: rs2506665187
Type: Deletion
Location: chr16:30721204 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1090: the 'disordered' region; a UniProt-annotated variant site (in dehmba)

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

Similar variants

SRCAP p.Pro2459fs Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Pro2461fs Pathogenic ★★ same type
SRCAP p.Ser2463fs Pathogenic ★★ same type
SRCAP p.Thr572del Uncertain significance ★★ same type
SRCAP p.Val1012del Uncertain significance ★★ same type
SRCAP p.Phe1867del Benign/Likely benign ★★ same type
SRCAP c.1187_1228+67del Likely pathogenic ★ same type
SRCAP c.1319del Pathogenic ★ 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/srcap-p-leu1090fs (accessed [today's date]).

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