Is AS3MT p.Ile321Thr (c.962T>C) pathogenic?

AS3MT p.Ile321Thr (c.962T>C) is classified Uncertain significance in AS3MT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.2875); Absent from gnomAD v4.1.

How common is AS3MT p.Ile321Thr (c.962T>C) in the general population?

AS3MT p.Ile321Thr (c.962T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AS3MT p.Ile321Thr (c.962T>C)?

AlphaMissense predicts likely benign (score 0.2875) — an in-silico prediction, not a clinical call.

AS3MT p.Ile321Thr

c.962T>C · rs1424241173 · VCV3130020

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2875 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2875	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -8.79	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 6.8	GERP 0.66, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 31 kb · p 0.0095 · regional, not allelic
Overall
CADD	22.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AS3MT
Protein: p.Ile321Thr
Coding: c.962T>C
MANE Select: NM_020682
dbSNP: rs1424241173
Type: single nucleotide variant
Location: chr10:102890620 (GRCh38)
Gene constraint: LOEUF 1.26 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.02 · 1 PDB
Residue 321: a β-strand

Full AS3MT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AS3MT p.Ala142Ser Uncertain significance ★ ⚠ same type
AS3MT p.Ala336Thr Uncertain significance ★ ⚠ same type
AS3MT p.Asp345Gly Uncertain significance ★ ⚠ same type
AS3MT p.Cys85Phe Uncertain significance ★ ⚠ same type
AS3MT p.Gln221Lys Uncertain significance ★ ⚠ same type
AS3MT p.Gln317Arg Uncertain significance ★ ⚠ same type
AS3MT p.Gln90His Uncertain significance ★ ⚠ same type
AS3MT p.Glu191Val 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/as3mt-p-ile321thr (accessed [today's date]).

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