Is SRCAP p.Arg940Gln (c.2819G>A) pathogenic?

SRCAP p.Arg940Gln (c.2819G>A) is classified Conflicting classifications of pathogenicity in SRCAP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-09-23). AlphaMissense: likely benign (0.0957); Very rare (popmax 0.00503%, amr); Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP p.Arg940Gln (c.2819G>A)?

SRCAP p.Arg940Gln (c.2819G>A) is associated with Floating-Harbor syndrome, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

How common is SRCAP p.Arg940Gln (c.2819G>A) in the general population?

SRCAP p.Arg940Gln (c.2819G>A) is very rare (popmax 0.00503%, amr) (gnomAD).

What do computational predictors say about SRCAP p.Arg940Gln (c.2819G>A)?

AlphaMissense predicts likely benign (score 0.0957) — an in-silico prediction, not a clinical call.

SRCAP p.Arg940Gln

c.2819G>A · rs571228447 · VCV1408359

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0957 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00503%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Floating-Harbor syndrome

Computational evidence

Protein change
AlphaMissense	0.0957	likely benign
REVEL	0.214	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	Δ0.98	acceptor gain · deltas
Pangolin	Δ0.79	gain · loss 0.04 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.2	GERP -0.62, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 4,608 bp · p 6.7e-06 · regional, not allelic
Overall
CADD	34.0	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 0.00503% Admixed American · 3/59,688 alleles

Filtering AF 0.00166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00143%

Overall 0.00212% 34/1,602,168 alleles · very rare exomes 32/1,449,874 · genomes 2/152,294 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00503%	19,896
European (non-Finnish)	0.00239%	41,792
Remaining individualsnot grpmax-eligible	0.00161%	61,996
African / African-American	0.00134%	74,854
South Asian	0.0011%	90,652

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.Arg940Gln
Coding: c.2819G>A
MANE Select: NM_006662
dbSNP: rs571228447
Type: single nucleotide variant
Location: chr16:30720163 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 940: 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

Also linked: developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

Similar variants

SRCAP p.Arg940Trp Uncertain significance ★ same residue
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

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-arg940gln (accessed [today's date]).

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