Is SRCAP p.Leu2593= (c.7777C>T) pathogenic?

SRCAP p.Leu2593= (c.7777C>T) is classified Benign/Likely benign in SRCAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-04). Rare (popmax 0.599%, eas); Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP p.Leu2593= (c.7777C>T)?

SRCAP p.Leu2593= (c.7777C>T) is associated with Floating-Harbor syndrome, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

How common is SRCAP p.Leu2593= (c.7777C>T) in the general population?

SRCAP p.Leu2593= (c.7777C>T) is rare (popmax 0.599%, eas) (gnomAD).

SRCAP p.Leu2593=

c.7777C>T · rs200333706 · VCV1581541

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.599%, eas)

Conditions

Floating-Harbor syndrome

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 1.6	GERP 0.38, phastCons 1
Overall
CADD	4.562	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.599% East Asian · 269/44,882 alleles

Filtering AF 0.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.518%

Overall 0.0212% 343/1,614,152 alleles · rare exomes 317/1,461,842 · genomes 26/152,310 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.599%	167
Remaining individualsnot grpmax-eligible	0.048%	2,084
South Asian	0.0362%	2,760
African / African-American	0.00133%	75,042
European (non-Finnish)	0.000847%	118,004

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.Leu2593=
Coding: c.7777C>T
MANE Select: NM_006662
dbSNP: rs200333706
Type: single nucleotide variant
Location: chr16:30737817 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2593: 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

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-p-leu2593 (accessed [today's date]).

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