Is SRCAP p.Arg318Ser (c.954G>T) pathogenic?

SRCAP p.Arg318Ser (c.954G>T) is classified Uncertain significance in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-05). AlphaMissense: likely benign (0.3307); Absent from gnomAD v4.1; Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP p.Arg318Ser (c.954G>T)?

SRCAP p.Arg318Ser (c.954G>T) is associated with Floating-Harbor syndrome (ClinVar).

How common is SRCAP p.Arg318Ser (c.954G>T) in the general population?

SRCAP p.Arg318Ser (c.954G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRCAP p.Arg318Ser (c.954G>T)?

AlphaMissense predicts likely benign (score 0.3307) — an in-silico prediction, not a clinical call.

SRCAP p.Arg318Ser

c.954G>T · rs2052869442 · VCV1030129

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3307 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Floating-Harbor syndrome

Computational evidence

Protein change
AlphaMissense	0.3307	likely benign
REVEL	0.506	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.63	GERP -2.4, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 127 bp · p 0.0011 · regional, not allelic
Overall
CADD	21.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SRCAP
Protein: p.Arg318Ser
Coding: c.954G>T
MANE Select: NM_006662
dbSNP: rs2052869442
Type: single nucleotide variant
Location: chr16:30709948 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 318: the 'disordered' region

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.Arg318Gly 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-arg318ser (accessed [today's date]).

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