Is SRCAP p.Leu2919Phe (c.8755C>T) pathogenic?

SRCAP p.Leu2919Phe (c.8755C>T) is classified Likely benign in SRCAP (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.0809); Rare (popmax 0.248%, mid); Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP p.Leu2919Phe (c.8755C>T)?

SRCAP p.Leu2919Phe (c.8755C>T) is associated with Floating-Harbor syndrome, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

How common is SRCAP p.Leu2919Phe (c.8755C>T) in the general population?

SRCAP p.Leu2919Phe (c.8755C>T) is rare (popmax 0.248%, mid) (gnomAD).

What do computational predictors say about SRCAP p.Leu2919Phe (c.8755C>T)?

AlphaMissense predicts likely benign (score 0.0809) — an in-silico prediction, not a clinical call.

SRCAP p.Leu2919Phe

c.8755C>T · rs149217909 · VCV160039

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.0809 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.248%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Floating-Harbor syndrome

Computational evidence

Protein change
AlphaMissense	0.0809	likely benign
REVEL	0.278	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · regional, not allelic
Overall
CADD	19.16	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.248% Middle Eastern · 15/6,056 alleles

Filtering AF 0.203% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.2%

Overall 0.171% 2,754/1,613,918 alleles · rare exomes 2,554/1,461,592 · genomes 200/152,326 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.248%	404
European (non-Finnish)	0.21%	476
Remaining individualsnot grpmax-eligible	0.173%	579
Admixed American	0.103%	968
South Asian	0.0494%	2,023
Finnishnot grpmax-eligible	0.0328%	3,049
African / African-American	0.028%	3,574
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,783

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.Leu2919Phe
Coding: c.8755C>T
MANE Select: NM_006662
dbSNP: rs149217909
Type: single nucleotide variant
Location: chr16:30738795 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2919: the 'disordered' 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

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-leu2919phe (accessed [today's date]).

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