Is AS3MT p.Leu88Phe (c.262C>T) pathogenic?

AS3MT p.Leu88Phe (c.262C>T) is classified Uncertain significance in AS3MT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.1777); Very rare (popmax 0.00401%, afr).

How common is AS3MT p.Leu88Phe (c.262C>T) in the general population?

AS3MT p.Leu88Phe (c.262C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about AS3MT p.Leu88Phe (c.262C>T)?

AlphaMissense predicts likely benign (score 0.1777) — an in-silico prediction, not a clinical call.

AS3MT p.Leu88Phe

c.262C>T · VCV3950403

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1777 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1777	likely benign
REVEL	0.241	benign-leaning
SaProt	LLR -9.35	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 -0.087	GERP -0.099
Regional constraint	o/e 0.88	unconstrained · MANE · 31 kb · p 0.0095 · regional, not allelic
Overall
CADD	20.4	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 0.00401% African / African-American · 3/74,890 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,613,848 alleles · very rare

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: AS3MT
Protein: p.Leu88Phe
Coding: c.262C>T
MANE Select: NM_020682
Type: single nucleotide variant
Location: chr10:102872539 (GRCh38)
Gene constraint: LOEUF 1.26 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.02 · 1 PDB
Residue 88: an α-helix

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-leu88phe (accessed [today's date]).

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