Is SRCAP p.Pro1759Ala (c.5275C>G) pathogenic?

SRCAP p.Pro1759Ala (c.5275C>G) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-20). AlphaMissense: likely benign (0.0567); Very rare (popmax 0.00833%, amr); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Pro1759Ala (c.5275C>G)?

SRCAP p.Pro1759Ala (c.5275C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Pro1759Ala (c.5275C>G) in the general population?

SRCAP p.Pro1759Ala (c.5275C>G) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about SRCAP p.Pro1759Ala (c.5275C>G)?

AlphaMissense predicts likely benign (score 0.0567) — an in-silico prediction, not a clinical call.

SRCAP p.Pro1759Ala

c.5275C>G · rs1263889163 · VCV2083134

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0567 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0567	likely benign
REVEL	0.301	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 1.5, phastCons 0.99
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	16.84	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 0.00833% Admixed American · 5/60,006 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000434% 7/1,613,954 alleles · very rare exomes 6/1,461,818 · genomes 1/152,136 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,001
European (non-Finnish)	0.000169%	590,012

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.Pro1759Ala
Coding: c.5275C>G
MANE Select: NM_006662
dbSNP: rs1263889163
Type: single nucleotide variant
Location: chr16:30724699 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1759: the 'disordered' region; 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-pro1759ala (accessed [today's date]).

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