Is SRCAP p.Lys2318Glu (c.6952A>G) pathogenic?

SRCAP p.Lys2318Glu (c.6952A>G) is classified Uncertain significance in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). AlphaMissense: ambiguous (0.5332); Absent from gnomAD v4.1; Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

How common is SRCAP p.Lys2318Glu (c.6952A>G) in the general population?

SRCAP p.Lys2318Glu (c.6952A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRCAP p.Lys2318Glu (c.6952A>G)?

AlphaMissense predicts ambiguous (score 0.5332) — an in-silico prediction, not a clinical call.

SRCAP p.Lys2318Glu

Q: What condition is associated with SRCAP p.Lys2318Glu (c.6952A>G)?

SRCAP p.Lys2318Glu (c.6952A>G) is associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome (ClinVar).

c.6952A>G · VCV3580197

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5332 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

Computational evidence

Protein change
AlphaMissense	0.5332	ambiguous
REVEL	0.412	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 918 bp · p 1.2e-06 · regional, not allelic
Overall
CADD	24.4	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.Lys2318Glu
Coding: c.6952A>G
MANE Select: NM_006662
Type: single nucleotide variant
Location: chr16:30736568 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2318: a UniProt-annotated variant site (in dehmba)

Full SRCAP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Floating-Harbor syndrome

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-lys2318glu (accessed [today's date]).

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