Is SRCAP p.Arg389Ser (c.1165C>A) pathogenic?

SRCAP p.Arg389Ser (c.1165C>A) is classified Likely benign in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-20). AlphaMissense: likely benign (0.2733); Ultra-rare (popmax 0.0557%, eas).

How common is SRCAP p.Arg389Ser (c.1165C>A) in the general population?

SRCAP p.Arg389Ser (c.1165C>A) is ultra-rare (popmax 0.0557%, eas) (gnomAD).

What do computational predictors say about SRCAP p.Arg389Ser (c.1165C>A)?

AlphaMissense predicts likely benign (score 0.2733) — an in-silico prediction, not a clinical call.

SRCAP p.Arg389Ser

c.1165C>A · rs376370021 · VCV1647684

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2733 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0557%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.2733	likely benign
REVEL	0.226	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>G here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.39	GERP -5.2
Regional constraint	o/e 0.95	unconstrained · MANE · 2,095 bp · p 0.41 · regional, not allelic
Overall
CADD	0.537	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 0.0557% East Asian · 25/44,890 alleles

Filtering AF 0.0387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.00167% 27/1,614,176 alleles · ultra-rare exomes 20/1,461,888 · genomes 7/152,288 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0557%	1,796
Remaining individualsnot grpmax-eligible	0.0032%	31,255

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.Arg389Ser
Coding: c.1165C>A
MANE Select: NM_006662
dbSNP: rs376370021
Type: single nucleotide variant
Location: chr16:30710784 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 389: the 'disordered' region

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

Similar variants

SRCAP p.Arg389Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
SRCAP p.Arg389His Conflicting classifications of pathogenicity ★ ⚠ same residue
SRCAP p.Arg389= Likely benign ★ same residue
SRCAP p.Arg389Leu Uncertain significance ★ same residue
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

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-arg389ser (accessed [today's date]).

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