Is SRCAP p.Arg972Pro (c.2915G>C) pathogenic?

SRCAP p.Arg972Pro (c.2915G>C) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-21). AlphaMissense: likely pathogenic (0.6588); Very rare (popmax 0.00891%, eas); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Arg972Pro (c.2915G>C)?

SRCAP p.Arg972Pro (c.2915G>C) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Arg972Pro (c.2915G>C) in the general population?

SRCAP p.Arg972Pro (c.2915G>C) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about SRCAP p.Arg972Pro (c.2915G>C)?

AlphaMissense predicts likely pathogenic (score 0.6588) — an in-silico prediction, not a clinical call.

SRCAP p.Arg972Pro

c.2915G>C · VCV3618247

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6588 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6588	likely pathogenic
REVEL	0.495	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.92 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 4,608 bp · p 6.7e-06 · regional, not allelic
Overall
CADD	25.1	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 0.00891% East Asian · 4/44,888 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000372% 6/1,614,168 alleles · very rare exomes 5/1,461,854 · genomes 1/152,314 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,222
Admixed American	0.00167%	60,020
European (non-Finnish)	8.47e-05%	1,180,013

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.Arg972Pro
Coding: c.2915G>C
MANE Select: NM_006662
Type: single nucleotide variant
Location: chr16:30720259 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 972: 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

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

Similar variants

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
SRCAP p.Ala2699Val Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala2945Val 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-arg972pro (accessed [today's date]).

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