Is SRCAP p.Gly2043Arg (c.6127G>A) pathogenic?

SRCAP p.Gly2043Arg (c.6127G>A) is classified Likely pathogenic in SRCAP (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9996); Very rare (popmax 8.47e-05%, nfe); Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

How common is SRCAP p.Gly2043Arg (c.6127G>A) in the general population?

SRCAP p.Gly2043Arg (c.6127G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about SRCAP p.Gly2043Arg (c.6127G>A)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

SRCAP p.Gly2043Arg

Q: What condition is associated with SRCAP p.Gly2043Arg (c.6127G>A)?

SRCAP p.Gly2043Arg (c.6127G>A) is associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

c.6127G>A · rs2053094101 · VCV1341679

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic ✓ concordant with ClinVar · top 3% in SRCAP
REVEL	0.803	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	Δ0.31	donor loss · deltas
Pangolin	Δ0.41	loss · gain 0.08 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 5,018 bp · p 2.4e-13 · regional, not allelic
Overall
CADD	34.0	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 8.47e-05% European (non-Finnish) · 1/1,180,012 alleles

Overall 6.2e-05% 1/1,614,070 alleles · very rare exomes 1/1,461,862 · genomes 0/152,208 · 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.Gly2043Arg
Coding: c.6127G>A
MANE Select: NM_006662
dbSNP: rs2053094101
Type: single nucleotide variant
Location: chr16:30729572 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2043: an α-helix; 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.Gly2043Val Uncertain significance ★★ ⚠ same residue
SRCAP p.Gly2043= 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

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-gly2043arg (accessed [today's date]).

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