Is SRCAP p.Thr2047Met (c.6140C>T) pathogenic?

SRCAP p.Thr2047Met (c.6140C>T) is classified Conflicting classifications of pathogenicity in SRCAP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-07-17). AlphaMissense: likely benign (0.3035); Ultra-rare (popmax 0.02%, afr); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Thr2047Met (c.6140C>T)?

SRCAP p.Thr2047Met (c.6140C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Thr2047Met (c.6140C>T) in the general population?

SRCAP p.Thr2047Met (c.6140C>T) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about SRCAP p.Thr2047Met (c.6140C>T)?

AlphaMissense predicts likely benign (score 0.3035) — an in-silico prediction, not a clinical call.

SRCAP p.Thr2047Met

c.6140C>T · rs144253022 · VCV1509770

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.3035 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3035	likely benign
REVEL	0.525	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 5,018 bp · p 2.4e-13 · regional, not allelic
Overall
CADD	24.5	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 0.02% African / African-American · 15/75,042 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00987%

Overall 0.00316% 51/1,613,912 alleles · ultra-rare exomes 38/1,461,598 · genomes 13/152,314 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0272%	3,677
African / African-Americangrpmax	0.02%	5,003
Middle Eastern	0.0166%	6,012
Admixed American	0.005%	20,007
East Asian	0.00446%	22,442
South Asian	0.00329%	30,361
European (non-Finnish)	0.000847%	118,002

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr2047Met
Coding: c.6140C>T
MANE Select: NM_006662
dbSNP: rs144253022
Type: single nucleotide variant
Location: chr16:30733292 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2047: an α-helix; the helicase c-terminal domain; 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.Thr2047= Likely benign ★ 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-thr2047met (accessed [today's date]).

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