Is SRCAP p.Cys1993fs (c.5977_5980del) pathogenic?

SRCAP p.Cys1993fs (c.59775980del) is classified Pathogenic/Likely pathogenic in SRCAP (ClinVar, No assertion criteria, 2 submitters; last evaluated 2021-11-08). No gnomAD frequency available for this variant; Associated with neurodevelopmental disorder.

What condition is associated with SRCAP p.Cys1993fs (c.5977_5980del)?

SRCAP p.Cys1993fs (c.5977_5980del) is associated with neurodevelopmental disorder, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

How common is SRCAP p.Cys1993fs (c.5977_5980del) in the general population?

SRCAP p.Cys1993fs (c.5977_5980del) is no gnomAD frequency available for this variant (gnomAD).

SRCAP p.Cys1993fs

c.5977_5980del · rs2151296560 · VCV995434

Pathogenic/Likely pathogenic No assertion criteria

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	predicted	premature termination codon in exon 27 of 34
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Cys1993fs
Coding: c.5977_5980del
MANE Select: NM_006662
dbSNP: rs2151296560
Type: Microsatellite
Location: chr16:30729418 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1993: a β-strand; a UniProt-annotated variant site (in dehmba)

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

Also linked: developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

Similar variants

SRCAP p.Gln2770del Uncertain significance ★★ same condition
SRCAP p.Glu3182del Uncertain significance ★★ same condition
SRCAP p.Pro2488del Uncertain significance ★★ same condition
SRCAP p.Ser2576del Uncertain significance ★★ same condition
SRCAP p.Arg2768_Gln2769insArg Uncertain significance ★ same condition
SRCAP p.Asp548del Uncertain significance ★ same condition
SRCAP p.Thr1147del Uncertain significance ★ same condition
SRCAP p.Leu1401fs Likely pathogenic 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-cys1993fs (accessed [today's date]).

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