Is SRCAP p.Arg1854Leu (c.5561G>T) pathogenic?

SRCAP p.Arg1854Leu (c.5561G>T) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-07). AlphaMissense: ambiguous (0.4415); Absent from gnomAD v4.1.

How common is SRCAP p.Arg1854Leu (c.5561G>T) in the general population?

SRCAP p.Arg1854Leu (c.5561G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRCAP p.Arg1854Leu (c.5561G>T)?

AlphaMissense predicts ambiguous (score 0.4415) — an in-silico prediction, not a clinical call.

SRCAP p.Arg1854Leu

c.5561G>T · rs746926335 · VCV1804195

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4415 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4415	ambiguous
REVEL	0.274	benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SRCAP
Protein: p.Arg1854Leu
Coding: c.5561G>T
MANE Select: NM_006662
dbSNP: rs746926335
Type: single nucleotide variant
Location: chr16:30724985 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1854: the 'disordered' region; a UniProt-annotated variant site (in dehmba)

Full SRCAP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SRCAP p.Arg1854Cys Uncertain significance ★ same residue
SRCAP p.Arg1854His Conflicting classifications of pathogenicity ★ same residue
SRCAP p.Arg1854= Likely benign ★ same residue
SRCAP p.Arg1854Pro Uncertain significance ★ same residue
SRCAP p.Arg2329Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2444Ter Pathogenic ★★ same type
SRCAP p.Arg2718Ter Pathogenic/Likely pathogenic ★★ same type

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-arg1854leu (accessed [today's date]).

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