Is STRN4 p.Ala403Ser (c.1207G>T) pathogenic?

STRN4 p.Ala403Ser (c.1207G>T) is classified Uncertain significance in STRN4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). AlphaMissense: likely pathogenic (0.7382); Absent from gnomAD v4.1.

How common is STRN4 p.Ala403Ser (c.1207G>T) in the general population?

STRN4 p.Ala403Ser (c.1207G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STRN4 p.Ala403Ser (c.1207G>T)?

AlphaMissense predicts likely pathogenic (score 0.7382) — an in-silico prediction, not a clinical call.

STRN4 p.Ala403Ser

c.1207G>T · VCV3323440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7382 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7382	likely pathogenic
REVEL	0.368	indeterminate
SaProt	LLR -7.69	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 21 kb · p 0.0069 · regional, not allelic
Overall
CADD	28.4	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

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: STRN4
Protein: p.Ala403Ser
Coding: c.1207G>T
MANE Select: NM_013403
Type: single nucleotide variant
Location: chr19:46727493 (GRCh38)
Gene constraint: LOEUF 0.523 · pLI 0.85 (gnomAD)
Structure: AlphaFold pLDDT 68.59

Full STRN4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FKRP c.-253+4A>G Uncertain significance ★★ same type
FKRP c.-253+5G>A Uncertain significance ★★ same type
STRN4 p.Pro158= Benign ★★ same type
FKRP c.-272G>A Conflicting classifications of pathogenicity ★ same type
STRN4 c.1154-14T>G Uncertain significance ★ same type
STRN4 c.1154-7T>C Uncertain significance ★ same type
STRN4 c.1907-1G>T Uncertain significance ★ same type
STRN4 c.737+1G>C 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/strn4-p-ala403ser (accessed [today's date]).

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