Is SRCAP p.Glu1890Val (c.5669A>T) pathogenic?

SRCAP p.Glu1890Val (c.5669A>T) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-14). AlphaMissense: likely pathogenic (0.9201); Very rare (popmax 0.000254%, nfe); Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

How common is SRCAP p.Glu1890Val (c.5669A>T) in the general population?

SRCAP p.Glu1890Val (c.5669A>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about SRCAP p.Glu1890Val (c.5669A>T)?

AlphaMissense predicts likely pathogenic (score 0.9201) — an in-silico prediction, not a clinical call.

SRCAP p.Glu1890Val

Q: What condition is associated with SRCAP p.Glu1890Val (c.5669A>T)?

SRCAP p.Glu1890Val (c.5669A>T) is associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

c.5669A>T · rs1319056235 · VCV2991471

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9201 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

Computational evidence

Protein change
AlphaMissense	0.9201	likely pathogenic
REVEL	0.533	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	23.6	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 0.000254% European (non-Finnish) · 3/1,179,120 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,612,868 alleles · very rare exomes 2/1,460,728 · genomes 1/152,140 · joint denominator

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.Glu1890Val
Coding: c.5669A>T
MANE Select: NM_006662
dbSNP: rs1319056235
Type: single nucleotide variant
Location: chr16:30728976 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1890: an α-helix; the 'disordered' region; 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

Similar variants

SRCAP p.Glu1890= Likely benign ★★ same residue
SRCAP p.Arg2444Ter Pathogenic ★★ same condition
SRCAP p.Arg2718Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP c.2130+6A>T Uncertain significance ★★ same condition
SRCAP c.492+3A>G Uncertain significance ★★ same condition
SRCAP p.Ala1161Thr Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1451Thr Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1461Val 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-glu1890val (accessed [today's date]).

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