Is SRCAP p.Leu2652Arg (c.7955T>G) pathogenic?

SRCAP p.Leu2652Arg (c.7955T>G) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-22). AlphaMissense: likely benign (0.13); Ultra-rare (popmax 0.0107%, afr); Associated with Monogenic short statue.

What condition is associated with SRCAP p.Leu2652Arg (c.7955T>G)?

SRCAP p.Leu2652Arg (c.7955T>G) is associated with Monogenic short statue (ClinVar).

How common is SRCAP p.Leu2652Arg (c.7955T>G) in the general population?

SRCAP p.Leu2652Arg (c.7955T>G) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about SRCAP p.Leu2652Arg (c.7955T>G)?

AlphaMissense predicts likely benign (score 0.13) — an in-silico prediction, not a clinical call.

SRCAP p.Leu2652Arg

c.7955T>G · VCV4174670

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.13 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Conditions

Monogenic short statue

Computational evidence

Protein change
AlphaMissense	0.13	likely benign
REVEL	0.37	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 2.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · regional, not allelic
Overall
CADD	23.4	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 0.0107% African / African-American · 8/74,886 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000558% 9/1,613,948 alleles · ultra-rare exomes 7/1,461,828 · genomes 2/152,120 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,361
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Leu2652Arg
Coding: c.7955T>G
MANE Select: NM_006662
Type: single nucleotide variant
Location: chr16:30737995 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2652: the 'disordered' region; a UniProt-annotated variant site (in dehmba); a UniProt-annotated variant site (in flhs)

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

Disease context

Monogenic short statue

Similar variants

SRCAP p.Leu2652= Likely benign ★ same residue
SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2444Ter Pathogenic ★★ same condition
SRCAP p.Arg2748Ter Pathogenic ★★ same condition
SRCAP p.Gln3043His Uncertain significance ★★ ⚠ same condition
SRCAP p.Gln3202His Uncertain significance ★★ same condition
SRCAP p.Pro1728Ala Uncertain significance ★★ ⚠ same condition
SRCAP p.Thr1745Met 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-leu2652arg (accessed [today's date]).

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