Is SRCAP p.Pro1762Gln (c.5285C>A) pathogenic?

SRCAP p.Pro1762Gln (c.5285C>A) is classified Uncertain significance in SRCAP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely benign (0.0947); Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with SRCAP p.Pro1762Gln (c.5285C>A)?

SRCAP p.Pro1762Gln (c.5285C>A) is associated with intellectual disability (ClinVar).

How common is SRCAP p.Pro1762Gln (c.5285C>A) in the general population?

SRCAP p.Pro1762Gln (c.5285C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRCAP p.Pro1762Gln (c.5285C>A)?

AlphaMissense predicts likely benign (score 0.0947) — an in-silico prediction, not a clinical call.

SRCAP p.Pro1762Gln

c.5285C>A · rs755651719 · VCV975471

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0947 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.0947	likely benign
REVEL	0.182	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 0.84	GERP -2.6, phastCons 0.001
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	14.38	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SRCAP
Protein: p.Pro1762Gln
Coding: c.5285C>A
MANE Select: NM_006662
dbSNP: rs755651719
Type: single nucleotide variant
Location: chr16:30724709 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1762: a UniProt-annotated variant site (in dehmba)

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SRCAP p.Arg2151His Uncertain significance ★ ⚠ same condition
SRCAP p.Thr1690Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
SRCAP p.Val1795Ile Uncertain significance ★ ⚠ same condition
SRCAP p.Arg2329Gln Likely benign ★ same condition
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-pro1762gln (accessed [today's date]).

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