Is STRN4 p.Arg491= (c.1473G>A) pathogenic?

STRN4 p.Arg491= (c.1473G>A) is classified Likely benign in STRN4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-21). Very rare (popmax 0.000254%, nfe).

How common is STRN4 p.Arg491= (c.1473G>A) in the general population?

STRN4 p.Arg491= (c.1473G>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

STRN4 p.Arg491=

c.1473G>A · rs771874482 · VCV2619954

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -3.5, phastCons 1
Overall
CADD	14.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,024 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,940 alleles · very rare exomes 3/1,461,586 · genomes 0/152,354 · joint denominator

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.Arg491=
Coding: c.1473G>A
MANE Select: NM_013403
dbSNP: rs771874482
Type: single nucleotide variant
Location: chr19:46724928 (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-arg491 (accessed [today's date]).

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