Is ARSI p.Arg381Trp (c.1141C>T) pathogenic?

ARSI p.Arg381Trp (c.1141C>T) is classified Uncertain significance in ARSI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-21). AlphaMissense: likely benign (0.1218); Very rare (popmax 0.00447%, eas).

How common is ARSI p.Arg381Trp (c.1141C>T) in the general population?

ARSI p.Arg381Trp (c.1141C>T) is very rare (popmax 0.00447%, eas) (gnomAD).

What do computational predictors say about ARSI p.Arg381Trp (c.1141C>T)?

AlphaMissense predicts likely benign (score 0.1218) — an in-silico prediction, not a clinical call.

ARSI p.Arg381Trp

c.1141C>T · VCV3949372

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1218 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1218	likely benign
REVEL	0.636	indeterminate
SaProt	LLR -10.12	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 5,156 bp · p 0.021 · regional, not allelic
Overall
CADD	26.6	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

Grpmax group 0.00447% East Asian · 2/44,708 alleles

Filtering AF 0.00292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00261%

Overall 0.0033% 53/1,604,922 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00447%	22,354
European (non-Finnish)	0.00383%	26,106
African / African-American	0.00268%	37,379
South Asian	0.00222%	45,078
Admixed American	0.00168%	59,582
Remaining individualsnot grpmax-eligible	0.00161%	62,060

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: ARSI
Protein: p.Arg381Trp
Coding: c.1141C>T
MANE Select: NM_001012301
Type: single nucleotide variant
Location: chr5:150297783 (GRCh38)
Gene constraint: LOEUF 1.403 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.35

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

Similar variants

ARSI p.Arg381Gln Uncertain significance ★★ ⚠ same residue
ARSI p.Ala216Thr Uncertain significance ★★ ⚠ same type
ARSI p.Ala259Val Uncertain significance ★★ ⚠ same type
ARSI p.Ala264Thr Uncertain significance ★★ ⚠ same type
ARSI p.Ala399Asp Uncertain significance ★★ ⚠ same type
ARSI p.Ala414Ser Uncertain significance ★★ ⚠ same type
ARSI p.Ala414Thr Uncertain significance ★★ ⚠ same type
ARSI p.Ala78Thr 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/arsi-p-arg381trp (accessed [today's date]).

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