Is SRCAP p.Val1403Met (c.4207G>A) pathogenic?

SRCAP p.Val1403Met (c.4207G>A) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-22). AlphaMissense: likely benign (0.1061); Ultra-rare (popmax 0.0165%, mid); Associated with Monogenic short statue.

What condition is associated with SRCAP p.Val1403Met (c.4207G>A)?

SRCAP p.Val1403Met (c.4207G>A) is associated with Monogenic short statue (ClinVar).

How common is SRCAP p.Val1403Met (c.4207G>A) in the general population?

SRCAP p.Val1403Met (c.4207G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about SRCAP p.Val1403Met (c.4207G>A)?

AlphaMissense predicts likely benign (score 0.1061) — an in-silico prediction, not a clinical call.

SRCAP p.Val1403Met

c.4207G>A · VCV3716023

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1061 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Monogenic short statue

Computational evidence

Protein change
AlphaMissense	0.1061	likely benign
REVEL	0.155	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP -0.23, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	14.79	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00143% 23/1,613,406 alleles · ultra-rare exomes 23/1,461,428 · genomes 0/151,978 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	0.00178%	56,172
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Val1403Met
Coding: c.4207G>A
MANE Select: NM_006662
Type: single nucleotide variant
Location: chr16:30723631 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1403: a UniProt-annotated variant site (in dehmba)

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

Disease context

Monogenic short statue

Similar variants

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.Leu2652Arg 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-val1403met (accessed [today's date]).

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