Is SRCAP p.Ser1290Gly (c.3868A>G) pathogenic?

SRCAP p.Ser1290Gly (c.3868A>G) is classified Benign/Likely benign in SRCAP (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-05-11). AlphaMissense: likely benign (0.1692); Low-frequency (popmax 1.22%, mid).

How common is SRCAP p.Ser1290Gly (c.3868A>G) in the general population?

SRCAP p.Ser1290Gly (c.3868A>G) is low-frequency (popmax 1.22%, mid) (gnomAD).

What do computational predictors say about SRCAP p.Ser1290Gly (c.3868A>G)?

AlphaMissense predicts likely benign (score 0.1692) — an in-silico prediction, not a clinical call.

SRCAP p.Ser1290Gly

c.3868A>G · rs150246733 · VCV218689

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1692 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.22%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1692	likely benign
REVEL	0.228	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	23.0	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 1.22% Middle Eastern · 74/6,054 alleles

Filtering AF 0.998% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.916%

Overall 0.0782% 1,260/1,612,270 alleles · low-frequency exomes 1,133/1,460,638 · genomes 127/151,632 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.22%	82
Ashkenazi Jewishnot grpmax-eligible	1.11%	90
Admixed American	0.17%	587
Remaining individualsnot grpmax-eligible	0.165%	606
European (non-Finnish)	0.0518%	1,930
African / African-American	0.0375%	2,670
South Asian	0.0154%	6,499

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.Ser1290Gly
Coding: c.3868A>G
MANE Select: NM_006662
dbSNP: rs150246733
Type: single nucleotide variant
Location: chr16:30722724 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1290: a UniProt-annotated variant site (in dehmba)

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

Similar variants

SRCAP p.Arg2329Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2444Ter Pathogenic ★★ same type
SRCAP p.Arg2718Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2748Ter Pathogenic ★★ same type
SRCAP p.Gln2407Ter Pathogenic ★★ same type
SRCAP p.Gln2419Ter Pathogenic ★★ same type
SRCAP p.Gln2665Ter Pathogenic/Likely pathogenic ★★ same type

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-ser1290gly (accessed [today's date]).

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