Is SORT1 p.His16Arg (c.47A>G) pathogenic?

SORT1 p.His16Arg (c.47A>G) is classified Uncertain significance in SORT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.0534); Very rare (popmax 0.00393%, eas).

How common is SORT1 p.His16Arg (c.47A>G) in the general population?

SORT1 p.His16Arg (c.47A>G) is very rare (popmax 0.00393%, eas) (gnomAD).

What do computational predictors say about SORT1 p.His16Arg (c.47A>G)?

AlphaMissense predicts likely benign (score 0.0534) — an in-silico prediction, not a clinical call.

SORT1 p.His16Arg

c.47A>G · VCV4171973

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0534 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00393%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0534	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -3.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.7	GERP -2.2, phastCons 0.93
Regional constraint	o/e 1.33	unconstrained · MANE · 304 bp · p 6.8e-05 · regional, not allelic
Overall
CADD	2.729	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 0.00393% East Asian · 1/25,446 alleles

Filtering AF 0.000145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000105%

Overall 0.000539% 7/1,298,096 alleles · very rare exomes 5/1,148,682 · genomes 2/149,414 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00393%	25,446
Admixed American	0.00293%	34,130
European (non-Finnish)	0.000494%	202,412

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: SORT1
Protein: p.His16Arg
Coding: c.47A>G
MANE Select: NM_002959
Type: single nucleotide variant
Location: chr1:109397846 (GRCh38)
Gene constraint: LOEUF 0.553 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 83.27 · 17 PDB

Full SORT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SORT1 p.Asp358Tyr Benign ★★ ⚠ same type
SORT1 p.Ser746Asn Benign ★★ same type
SORT1 p.Ala340Thr Uncertain significance ★ ⚠ same type
SORT1 p.Arg288Lys Uncertain significance ★ ⚠ same type
SORT1 p.Arg311His Uncertain significance ★ ⚠ same type
SORT1 p.Arg326Ser Uncertain significance ★ ⚠ same type
SORT1 p.Arg382Gln Uncertain significance ★ ⚠ same type
SORT1 p.Arg392Leu 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/sort1-p-his16arg (accessed [today's date]).

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