Is STRN4 p.Ser35Pro (c.103T>C) pathogenic?

STRN4 p.Ser35Pro (c.103T>C) is classified Uncertain significance in STRN4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely benign (0.0578); Rare (popmax 0.154%, eas).

How common is STRN4 p.Ser35Pro (c.103T>C) in the general population?

STRN4 p.Ser35Pro (c.103T>C) is rare (popmax 0.154%, eas) (gnomAD).

What do computational predictors say about STRN4 p.Ser35Pro (c.103T>C)?

AlphaMissense predicts likely benign (score 0.0578) — an in-silico prediction, not a clinical call.

STRN4 p.Ser35Pro

c.103T>C · rs1427783096 · VCV3171662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0578 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.154%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0578	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -3.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.92	GERP -1.2, phastCons 0.3
Regional constraint	o/e 0.89	unconstrained · MANE · 21 kb · p 0.0069 · regional, not allelic
Overall
CADD	16.72	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 0.154% East Asian · 46/29,778 alleles

Filtering AF 0.119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.106%

Overall 0.0036% 47/1,305,522 alleles · rare exomes 46/1,157,958 · genomes 1/147,564 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.154%	647
Remaining individualsnot grpmax-eligible	0.00207%	48,274

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: STRN4
Protein: p.Ser35Pro
Coding: c.103T>C
MANE Select: NM_013403
dbSNP: rs1427783096
Type: single nucleotide variant
Location: chr19:46746328 (GRCh38)

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

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-ser35pro (accessed [today's date]).

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