Is STRADB p.Ala46Val (c.137C>T) pathogenic?

STRADB p.Ala46Val (c.137C>T) is classified Uncertain significance in STRADB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). AlphaMissense: likely benign (0.0826); Very rare (popmax 0.000169%, nfe).

How common is STRADB p.Ala46Val (c.137C>T) in the general population?

STRADB p.Ala46Val (c.137C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about STRADB p.Ala46Val (c.137C>T)?

AlphaMissense predicts likely benign (score 0.0826) — an in-silico prediction, not a clinical call.

STRADB p.Ala46Val

c.137C>T · rs1207032976 · VCV2297675

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0826 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0826	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.26	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 3	GERP 1.1, phastCons 0.97
Regional constraint	o/e 0.70	unconstrained · MANE · 25 kb · p 6e-11 · regional, not allelic
Overall
CADD	13.58	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,964 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00131% 2/152,140 alleles · very rare

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: STRADB
Protein: p.Ala46Val
Coding: c.137C>T
MANE Select: NM_018571
dbSNP: rs1207032976
Type: single nucleotide variant
Location: chr2:201469996 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.39

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

Similar variants

STRADB p.Ala103Pro Uncertain significance ★ ⚠ same type
STRADB p.Arg100Cys Uncertain significance ★ ⚠ same type
STRADB p.Arg100Leu Uncertain significance ★ ⚠ same type
STRADB p.Arg115Trp Uncertain significance ★ ⚠ same type
STRADB p.Arg329Gln Uncertain significance ★ ⚠ same type
STRADB p.Arg41Cys Uncertain significance ★ ⚠ same type
STRADB p.Asn163Ser Uncertain significance ★ ⚠ same type
STRADB p.Asp250Gly Uncertain significance ★ ⚠ 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/stradb-p-ala46val (accessed [today's date]).

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