Is STRADB p.Ala103Pro (c.307G>C) pathogenic?

STRADB p.Ala103Pro (c.307G>C) is classified Uncertain significance in STRADB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). AlphaMissense: likely pathogenic (0.7305); Ultra-rare (popmax 0.0179%, eas).

How common is STRADB p.Ala103Pro (c.307G>C) in the general population?

STRADB p.Ala103Pro (c.307G>C) is ultra-rare (popmax 0.0179%, eas) (gnomAD).

What do computational predictors say about STRADB p.Ala103Pro (c.307G>C)?

AlphaMissense predicts likely pathogenic (score 0.7305) — an in-silico prediction, not a clinical call.

STRADB p.Ala103Pro

c.307G>C · VCV3963565

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7305 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7305	likely pathogenic
REVEL	0.406	indeterminate
SaProt	LLR -9.98	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 0.47, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 25 kb · p 6e-11 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0179% East Asian · 8/44,778 alleles

Filtering AF 0.00885% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00642%

Overall 0.000558% 9/1,611,766 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0179%	5,597
European (non-Finnish)	8.48e-05%	1,179,391

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.Ala103Pro
Coding: c.307G>C
MANE Select: NM_018571
Type: single nucleotide variant
Location: chr2:201473068 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.39
Residue 103: the protein kinase domain

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

Similar variants

STRADB p.Ala46Val 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-ala103pro (accessed [today's date]).

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