Is SRCAP p.Ile1397Val (c.4189A>G) pathogenic?

SRCAP p.Ile1397Val (c.4189A>G) is classified Conflicting classifications of pathogenicity in SRCAP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-17). AlphaMissense: likely benign (0.0927); Rare (popmax 0.421%, afr).

How common is SRCAP p.Ile1397Val (c.4189A>G) in the general population?

SRCAP p.Ile1397Val (c.4189A>G) is rare (popmax 0.421%, afr) (gnomAD).

What do computational predictors say about SRCAP p.Ile1397Val (c.4189A>G)?

AlphaMissense predicts likely benign (score 0.0927) — an in-silico prediction, not a clinical call.

SRCAP p.Ile1397Val

c.4189A>G · rs144657822 · VCV283553

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0927 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.421%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0927	likely benign
REVEL	0.153	moderately 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 7.9	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	13.0	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 0.421% African / African-American · 315/74,806 alleles

Filtering AF 0.383% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.368%

Overall 0.0286% 462/1,613,116 alleles · rare exomes 272/1,461,448 · genomes 190/151,668 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.421%	237
Ashkenazi Jewishnot grpmax-eligible	0.156%	643
Admixed American	0.045%	2,220
Remaining individualsnot grpmax-eligible	0.0352%	2,839
Middle Eastern	0.033%	3,029
South Asian	0.011%	9,100
European (non-Finnish)	0.00339%	29,491

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.Ile1397Val
Coding: c.4189A>G
MANE Select: NM_006662
dbSNP: rs144657822
Type: single nucleotide variant
Location: chr16:30723613 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1397: 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-ile1397val (accessed [today's date]).

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