Is SRCAP p.Thr1727Ala (c.5179A>G) pathogenic?

SRCAP p.Thr1727Ala (c.5179A>G) is classified Conflicting classifications of pathogenicity in SRCAP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-07-20). AlphaMissense: likely benign (0.056); Very rare (popmax 0.00501%, amr); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Thr1727Ala (c.5179A>G)?

SRCAP p.Thr1727Ala (c.5179A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Thr1727Ala (c.5179A>G) in the general population?

SRCAP p.Thr1727Ala (c.5179A>G) is very rare (popmax 0.00501%, amr) (gnomAD).

What do computational predictors say about SRCAP p.Thr1727Ala (c.5179A>G)?

AlphaMissense predicts likely benign (score 0.056) — an in-silico prediction, not a clinical call.

SRCAP p.Thr1727Ala

c.5179A>G · VCV3322573

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.056 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.056	likely benign
REVEL	0.216	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 -0.57	GERP -4.3
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	8.28	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 0.00501% Admixed American · 3/59,934 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000744% 12/1,613,140 alleles · very rare exomes 12/1,461,894 · genomes 0/151,246 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,978
East Asian	0.00447%	22,371
South Asian	0.00439%	22,758
Remaining individualsnot grpmax-eligible	0.0016%	62,490
African / African-American	0.00134%	74,680
European (non-Finnish)	8.48e-05%	1,179,805

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.Thr1727Ala
Coding: c.5179A>G
MANE Select: NM_006662
Type: single nucleotide variant
Location: chr16:30724603 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1727: 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.Thr1727Pro Uncertain significance ★ ⚠ 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
SRCAP p.Ala2699Val 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-thr1727ala (accessed [today's date]).

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