Is SRCAP c.5658+15C>T pathogenic?

SRCAP c.5658+15C>T is classified Likely benign in SRCAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-02). Very rare (popmax 0.0048%, nfe); Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP c.5658+15C>T?

SRCAP c.5658+15C>T is associated with Floating-Harbor syndrome, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

How common is SRCAP c.5658+15C>T in the general population?

SRCAP c.5658+15C>T is very rare (popmax 0.0048%, nfe) (gnomAD).

SRCAP c.5658+15C>T

rs775744605 · VCV1661118

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0048%, nfe)

Conditions

Floating-Harbor syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +15	near-intronic (+15 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.066	GERP -4.2
Non-coding constraint	Z -0.91	1 kb window · o/e 1.06 · regional · uncalibrated
Overall
CADD	4.601	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0048% European (non-Finnish) · 56/1,167,328 alleles

Filtering AF 0.00379% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00341%

Overall 0.00352% 56/1,590,058 alleles · very rare exomes 48/1,437,920 · genomes 8/152,138 · 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
Coding: c.5658+15C>T
MANE Select: NM_006662
dbSNP: rs775744605
Type: single nucleotide variant
Location: chr16:30725097 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Disease context

Floating-Harbor syndrome — 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.Arg2329Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2444Ter Pathogenic ★★ same condition
SRCAP p.Arg2718Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2748Ter Pathogenic ★★ same condition
SRCAP p.Gln2407Ter Pathogenic ★★ same condition
SRCAP p.Gln2419Ter Pathogenic ★★ same condition
SRCAP p.Gln2665Ter Pathogenic/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-c-5658-plus-15c-t (accessed [today's date]).

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