Is SRCAP p.Ala2892= (c.8676T>G) pathogenic?

SRCAP p.Ala2892= (c.8676T>G) is classified Likely benign in SRCAP (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-10-14). Ultra-rare (popmax 0.0637%, nfe); Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP p.Ala2892= (c.8676T>G)?

SRCAP p.Ala2892= (c.8676T>G) is associated with Floating-Harbor syndrome, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

How common is SRCAP p.Ala2892= (c.8676T>G) in the general population?

SRCAP p.Ala2892= (c.8676T>G) is ultra-rare (popmax 0.0637%, nfe) (gnomAD).

SRCAP p.Ala2892=

c.8676T>G · rs140675498 · VCV318907

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0637%, nfe)

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 -0.5	GERP -2.4, phastCons 0.13
Overall
CADD	2.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0637% European (non-Finnish) · 752/1,180,024 alleles

Filtering AF 0.0599% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0584%

Overall 0.0514% 829/1,614,018 alleles · ultra-rare exomes 770/1,461,840 · genomes 59/152,178 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0637%	1,569
Remaining individualsnot grpmax-eligible	0.0512%	1,953
Admixed American	0.05%	2,000
Finnishnot grpmax-eligible	0.0125%	8,005
African / African-American	0.00934%	10,703

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.Ala2892=
Coding: c.8676T>G
MANE Select: NM_006662
dbSNP: rs140675498
Type: single nucleotide variant
Location: chr16:30738716 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2892: 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-ala2892 (accessed [today's date]).

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