Is SRCAP p.Val1085Ala (c.3254T>C) pathogenic?

SRCAP p.Val1085Ala (c.3254T>C) is classified Conflicting classifications of pathogenicity in SRCAP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-04-05). AlphaMissense: likely benign (0.1876); Ultra-rare (popmax 0.05%, mid); Associated with Inborn genetic diseases.

How common is SRCAP p.Val1085Ala (c.3254T>C) in the general population?

SRCAP p.Val1085Ala (c.3254T>C) is ultra-rare (popmax 0.05%, mid) (gnomAD).

What do computational predictors say about SRCAP p.Val1085Ala (c.3254T>C)?

AlphaMissense predicts likely benign (score 0.1876) — an in-silico prediction, not a clinical call.

SRCAP p.Val1085Ala

Q: What condition is associated with SRCAP p.Val1085Ala (c.3254T>C)?

SRCAP p.Val1085Ala (c.3254T>C) is associated with Inborn genetic diseases, Floating-Harbor syndrome, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

c.3254T>C · rs200083101 · VCV1359277

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1876 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.05%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1876	likely benign
REVEL	0.318	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	23.3	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 0.05% Middle Eastern · 3/5,996 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00726%

Overall 0.00462% 74/1,602,380 alleles · ultra-rare exomes 65/1,450,076 · genomes 9/152,304 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.05%	1,999
Remaining individualsnot grpmax-eligible	0.00645%	15,501
European (non-Finnish)	0.00571%	17,517

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.Val1085Ala
Coding: c.3254T>C
MANE Select: NM_006662
dbSNP: rs200083101
Type: single nucleotide variant
Location: chr16:30721189 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1085: 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

Also linked: Floating-Harbor syndrome developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

Similar variants

SRCAP p.Arg2329Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2444Ter Pathogenic ★★ same condition
SRCAP p.Arg2718Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2748Ter Pathogenic ★★ same condition
SRCAP p.Gln2407Ter Pathogenic ★★ same condition
SRCAP p.Gln2419Ter Pathogenic ★★ same condition
SRCAP p.Gln2665Ter Pathogenic/Likely pathogenic ★★ 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-val1085ala (accessed [today's date]).

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