Is SRCAP p.Thr918Pro (c.2752A>C) pathogenic?

SRCAP p.Thr918Pro (c.2752A>C) is classified Likely benign in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-28). AlphaMissense: likely pathogenic (0.7462); Ultra-rare (popmax 0.099%, mid); Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP p.Thr918Pro (c.2752A>C)?

SRCAP p.Thr918Pro (c.2752A>C) is associated with Floating-Harbor syndrome (ClinVar).

How common is SRCAP p.Thr918Pro (c.2752A>C) in the general population?

SRCAP p.Thr918Pro (c.2752A>C) is ultra-rare (popmax 0.099%, mid) (gnomAD).

What do computational predictors say about SRCAP p.Thr918Pro (c.2752A>C)?

AlphaMissense predicts likely pathogenic (score 0.7462) — an in-silico prediction, not a clinical call.

SRCAP p.Thr918Pro

c.2752A>C · rs756223991 · VCV803249

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7462 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.099%, mid)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Floating-Harbor syndrome

Computational evidence

Protein change
AlphaMissense	0.7462	likely pathogenic
REVEL	0.772	pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	Δ0.30	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.4	GERP 2.7, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 4,608 bp · p 6.7e-06 · regional, not allelic
Overall
CADD	26.2	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 0.099% Middle Eastern · 6/6,062 alleles

Filtering AF 0.0911% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0893%

Overall 0.0828% 1,334/1,611,014 alleles · ultra-rare exomes 1,323/1,459,220 · genomes 11/151,794 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.158%	632
Ashkenazi Jewishnot grpmax-eligible	0.102%	983
Remaining individualsnot grpmax-eligible	0.0994%	1,006
Middle Easterngrpmax	0.099%	1,010
European (non-Finnish)	0.0959%	1,043
South Asian	0.00329%	30,356
African / African-American	0.00267%	37,403
Admixed American	0.00167%	59,950

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr918Pro
Coding: c.2752A>C
MANE Select: NM_006662
dbSNP: rs756223991
Type: single nucleotide variant
Location: chr16:30716414 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 918: a UniProt-annotated variant site (in dehmba)

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

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-thr918pro (accessed [today's date]).

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