Is SRCAP p.Lys2865fs (c.8592dup) pathogenic?

SRCAP p.Lys2865fs (c.8592dup) is classified Likely pathogenic in SRCAP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-01-10). No allele count reported in gnomAD v4.1 (AN 1,605,786); Associated with neurodevelopmental disorder.

What condition is associated with SRCAP p.Lys2865fs (c.8592dup)?

SRCAP p.Lys2865fs (c.8592dup) is associated with neurodevelopmental disorder (ClinVar).

How common is SRCAP p.Lys2865fs (c.8592dup) in the general population?

SRCAP p.Lys2865fs (c.8592dup) is no allele count reported in gnomAD v4.1 (AN 1,605,786) (gnomAD).

SRCAP p.Lys2865fs

c.8592dup · rs2053186315 · VCV995443

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,605,786)

Conditions

neurodevelopmental disorder

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	escapes	premature termination codon in the last exon (34 of 34) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3	GERP 1.1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,605,786). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SRCAP
Protein: p.Lys2865fs
Coding: c.8592dup
MANE Select: NM_006662
dbSNP: rs2053186315
Type: Duplication
Location: chr16:30738626 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2865: the 'disordered' region; a DNA-binding region; a UniProt-annotated variant site (in dehmba); a UniProt-annotated variant site (in flhs)

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

Disease context

neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SRCAP p.Pro1879fs Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Gln3043fs Likely pathogenic same condition
SRCAP p.Glu2301fs Pathogenic ★ same condition
SRCAP p.His50fs Pathogenic ★ same condition
SRCAP p.Leu3113fs Likely pathogenic ★ same condition
SRCAP p.Pro278fs Pathogenic ★ same condition
SRCAP p.Ser1278Ter Likely pathogenic ★ same condition
SRCAP p.Gln1519fs 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/srcap-p-lys2865fs (accessed [today's date]).

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