Is SRCAP p.Ile1972Thr (c.5915T>C) pathogenic?

SRCAP p.Ile1972Thr (c.5915T>C) is classified Uncertain significance in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). AlphaMissense: likely pathogenic (0.8787); Very rare (popmax 8.51e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Ile1972Thr (c.5915T>C)?

SRCAP p.Ile1972Thr (c.5915T>C) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Ile1972Thr (c.5915T>C) in the general population?

SRCAP p.Ile1972Thr (c.5915T>C) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

What do computational predictors say about SRCAP p.Ile1972Thr (c.5915T>C)?

AlphaMissense predicts likely pathogenic (score 0.8787) — an in-silico prediction, not a clinical call.

SRCAP p.Ile1972Thr

c.5915T>C · rs1368909848 · VCV2298086

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8787 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8787	likely pathogenic
REVEL	0.542	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	23.6	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 8.51e-05% European (non-Finnish) · 1/1,174,722 alleles

Overall 6.22e-05% 1/1,606,648 alleles · very rare exomes 1/1,454,362 · genomes 0/152,286 · joint denominator

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.Ile1972Thr
Coding: c.5915T>C
MANE Select: NM_006662
dbSNP: rs1368909848
Type: single nucleotide variant
Location: chr16:30729222 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1972: 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-ile1972thr (accessed [today's date]).

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