Is SRCAP p.Arg2794Cys (c.8380C>T) pathogenic?

SRCAP p.Arg2794Cys (c.8380C>T) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-31). AlphaMissense: likely benign (0.0789); Very rare (popmax 0.00685%, afr); Associated with Inborn genetic diseases.

How common is SRCAP p.Arg2794Cys (c.8380C>T) in the general population?

SRCAP p.Arg2794Cys (c.8380C>T) is very rare (popmax 0.00685%, afr) (gnomAD).

What do computational predictors say about SRCAP p.Arg2794Cys (c.8380C>T)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

SRCAP p.Arg2794Cys

Q: What condition is associated with SRCAP p.Arg2794Cys (c.8380C>T)?

SRCAP p.Arg2794Cys (c.8380C>T) is associated with Inborn genetic diseases, Floating-Harbor syndrome, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

c.8380C>T · rs139190108 · VCV196911

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00685%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.6	GERP 2.4, phastCons 0.58
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · regional, not allelic
Overall
CADD	17.09	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00685% African / African-American · 5/73,014 alleles

Filtering AF 0.0026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00165%

Overall 0.000644% 10/1,552,596 alleles · very rare exomes 6/1,400,436 · genomes 4/152,160 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00685%	14,603
East Asian	0.00225%	44,366
Admixed American	0.00194%	51,504
Remaining individualsnot grpmax-eligible	0.00167%	59,730
European (non-Finnish)	0.000174%	574,604

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.Arg2794Cys
Coding: c.8380C>T
MANE Select: NM_006662
dbSNP: rs139190108
Type: single nucleotide variant
Location: chr16:30738420 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2794: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Floating-Harbor syndrome developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

Similar variants

SRCAP p.Arg2794His Likely benign ★★ same residue
SRCAP p.Arg2794Leu 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

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-arg2794cys (accessed [today's date]).

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