Is SRCAP p.Met2028Val (c.6082A>G) pathogenic?

SRCAP p.Met2028Val (c.6082A>G) is classified Conflicting classifications of pathogenicity in SRCAP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-16). AlphaMissense: likely pathogenic (0.819); Ultra-rare (popmax 0.0194%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Met2028Val (c.6082A>G)?

SRCAP p.Met2028Val (c.6082A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Met2028Val (c.6082A>G) in the general population?

SRCAP p.Met2028Val (c.6082A>G) is ultra-rare (popmax 0.0194%, nfe) (gnomAD).

What do computational predictors say about SRCAP p.Met2028Val (c.6082A>G)?

AlphaMissense predicts likely pathogenic (score 0.819) — an in-silico prediction, not a clinical call.

SRCAP p.Met2028Val

c.6082A>G · rs147650424 · VCV2469834

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.819 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0194%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.819	likely pathogenic
REVEL	0.527	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 5,018 bp · p 2.4e-13 · regional, not allelic
Overall
CADD	22.7	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 0.0194% European (non-Finnish) · 229/1,180,050 alleles

Filtering AF 0.0173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0165%

Overall 0.0149% 241/1,614,064 alleles · ultra-rare exomes 225/1,461,894 · genomes 16/152,170 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0194%	5,153
Remaining individualsnot grpmax-eligible	0.0096%	10,414
African / African-American	0.00667%	14,983
Finnishnot grpmax-eligible	0.00156%	64,032

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.Met2028Val
Coding: c.6082A>G
MANE Select: NM_006662
dbSNP: rs147650424
Type: single nucleotide variant
Location: chr16:30729527 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2028: 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.Met2028Thr 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-met2028val (accessed [today's date]).

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