Is SRCAP p.Ser1468Trp (c.4403C>G) pathogenic?

SRCAP p.Ser1468Trp (c.4403C>G) is classified Uncertain significance in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.2493); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Ser1468Trp (c.4403C>G)?

SRCAP p.Ser1468Trp (c.4403C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Ser1468Trp (c.4403C>G) in the general population?

SRCAP p.Ser1468Trp (c.4403C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRCAP p.Ser1468Trp (c.4403C>G)?

AlphaMissense predicts likely benign (score 0.2493) — an in-silico prediction, not a clinical call.

SRCAP p.Ser1468Trp

c.4403C>G · VCV3961848

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2493 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2493	likely benign
REVEL	0.25	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	22.5	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

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.Ser1468Trp
Coding: c.4403C>G
MANE Select: NM_006662
Type: single nucleotide variant
Location: chr16:30723827 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1468: a UniProt-annotated variant site (in dehmba)

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

Similar variants

SRCAP p.Ser1468= Likely benign ★ same residue
SRCAP p.Ser1468Leu Benign ★ same residue
SRCAP p.Gln2407Ter Pathogenic ★★ same condition
SRCAP p.Ala1152Val Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1161Thr Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1570Thr Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1584Gly Uncertain significance ★★ same condition
SRCAP p.Ala1985Thr Uncertain significance ★★ 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-ser1468trp (accessed [today's date]).

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