Is SRCAP p.Pro3130Gln (c.9389C>A) pathogenic?

SRCAP p.Pro3130Gln (c.9389C>A) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-04). AlphaMissense: likely pathogenic (0.6997); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Pro3130Gln (c.9389C>A)?

SRCAP p.Pro3130Gln (c.9389C>A) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Pro3130Gln (c.9389C>A) in the general population?

SRCAP p.Pro3130Gln (c.9389C>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about SRCAP p.Pro3130Gln (c.9389C>A)?

AlphaMissense predicts likely pathogenic (score 0.6997) — an in-silico prediction, not a clinical call.

SRCAP p.Pro3130Gln

c.9389C>A · rs754639611 · VCV2720084

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6997 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6997	likely pathogenic
REVEL	0.496	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · regional, not allelic
Overall
CADD	24.5	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 0.00223% East Asian · 1/44,896 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000929% 15/1,614,096 alleles · very rare exomes 11/1,461,856 · genomes 4/152,240 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Remaining individualsnot grpmax-eligible	0.0032%	31,244
East Asiangrpmax	0.00223%	44,896
European (non-Finnish)	0.000932%	107,276

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro3130Gln
Coding: c.9389C>A
MANE Select: NM_006662
dbSNP: rs754639611
Type: single nucleotide variant
Location: chr16:30739429 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3130: the 'disordered' region; a UniProt-annotated variant site (in dehmba); a UniProt-annotated variant site (in flhs)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SRCAP p.Pro3130Leu Uncertain significance ★★ same residue
SRCAP p.Pro3130= Likely benign ★★ same residue
SRCAP p.Gln2407Ter Pathogenic ★★ same condition
SRCAP p.Ala1152Val Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1161Thr Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1570Thr Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1584Gly Uncertain significance ★★ same condition
SRCAP p.Ala1985Thr 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-pro3130gln (accessed [today's date]).

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