Is SRCAP p.Arg858Cys (c.2572C>T) pathogenic?

SRCAP p.Arg858Cys (c.2572C>T) is classified Conflicting classifications of pathogenicity in SRCAP (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-02-16). AlphaMissense: likely benign (0.1862); Ultra-rare (popmax 0.0495%, mid); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Arg858Cys (c.2572C>T)?

SRCAP p.Arg858Cys (c.2572C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Arg858Cys (c.2572C>T) in the general population?

SRCAP p.Arg858Cys (c.2572C>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about SRCAP p.Arg858Cys (c.2572C>T)?

AlphaMissense predicts likely benign (score 0.1862) — an in-silico prediction, not a clinical call.

SRCAP p.Arg858Cys

c.2572C>T · rs200723469 · VCV2177003

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1862 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1862	likely benign
REVEL	0.594	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 4,608 bp · p 6.7e-06 · regional, not allelic
Overall
CADD	29.4	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 0.0495% Middle Eastern · 3/6,060 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.0113% 182/1,614,142 alleles · ultra-rare exomes 170/1,461,886 · genomes 12/152,256 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,020
European (non-Finnish)	0.0136%	7,375
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.00833%	12,004
Finnishnot grpmax-eligible	0.00625%	16,004
East Asian	0.00223%	44,888
South Asian	0.0011%	91,082

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.Arg858Cys
Coding: c.2572C>T
MANE Select: NM_006662
dbSNP: rs200723469
Type: single nucleotide variant
Location: chr16:30716144 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 858: a β-strand; 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.Arg858His Conflicting classifications of pathogenicity ★ same residue
SRCAP p.Arg858= 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

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-arg858cys (accessed [today's date]).

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