Is STRN4 p.Pro19Gln (c.56C>A) pathogenic?

STRN4 p.Pro19Gln (c.56C>A) is classified Uncertain significance in STRN4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-03). AlphaMissense: likely benign (0.1044); Ultra-rare (popmax 0.0213%, sas).

How common is STRN4 p.Pro19Gln (c.56C>A) in the general population?

STRN4 p.Pro19Gln (c.56C>A) is ultra-rare (popmax 0.0213%, sas) (gnomAD).

What do computational predictors say about STRN4 p.Pro19Gln (c.56C>A)?

AlphaMissense predicts likely benign (score 0.1044) — an in-silico prediction, not a clinical call.

STRN4 p.Pro19Gln

c.56C>A · rs1462958696 · VCV2205400

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1044 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, sas)

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	0.1044	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -8.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.7	GERP -0.47, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 21 kb · p 0.0069 · regional, not allelic
Overall
CADD	22.4	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 0.0213% South Asian · 5/23,518 alleles

Filtering AF 0.00835% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00539%

Overall 0.0007% 8/1,142,814 alleles · ultra-rare exomes 3/996,494 · genomes 5/146,320 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0213%	4,704
African / African-American	0.00332%	30,112
Remaining individualsnot grpmax-eligible	0.00253%	39,510

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.Pro19Gln
Coding: c.56C>A
MANE Select: NM_013403
dbSNP: rs1462958696
Type: single nucleotide variant
Location: chr19:46746375 (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-pro19gln (accessed [today's date]).

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