Is SRCAP p.Leu2052Phe (c.6156G>C) pathogenic?

SRCAP p.Leu2052Phe (c.6156G>C) is classified Uncertain significance in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-08). AlphaMissense: likely pathogenic (0.9845); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Leu2052Phe (c.6156G>C)?

SRCAP p.Leu2052Phe (c.6156G>C) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Leu2052Phe (c.6156G>C) in the general population?

SRCAP p.Leu2052Phe (c.6156G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRCAP p.Leu2052Phe (c.6156G>C)?

AlphaMissense predicts likely pathogenic (score 0.9845) — an in-silico prediction, not a clinical call.

SRCAP p.Leu2052Phe

c.6156G>C · rs1555465595 · VCV2259155

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9845 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9845	likely pathogenic
REVEL	0.587	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP -3, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 5,018 bp · p 2.4e-13 · regional, not allelic
Overall
CADD	20.6	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.Leu2052Phe
Coding: c.6156G>C
MANE Select: NM_006662
dbSNP: rs1555465595
Type: single nucleotide variant
Location: chr16:30733308 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2052: 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.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
SRCAP p.Ala2945Val 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-leu2052phe (accessed [today's date]).

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