Is AMY2A p.Val104Asp (c.311T>A) pathogenic?

AMY2A p.Val104Asp (c.311T>A) is classified Uncertain significance in AMY2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: likely pathogenic (0.6063); Absent from gnomAD v4.1.

How common is AMY2A p.Val104Asp (c.311T>A) in the general population?

AMY2A p.Val104Asp (c.311T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMY2A p.Val104Asp (c.311T>A)?

AlphaMissense predicts likely pathogenic (score 0.6063) — an in-silico prediction, not a clinical call.

AMY2A p.Val104Asp

c.311T>A · VCV3536942

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6063 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6063	likely pathogenic
REVEL	0.94	strongly pathogenic-leaning
SaProt	LLR -13.96	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP 1.7, phastCons 0.93
Regional constraint	o/e 0.94	unconstrained · MANE · 1,667 bp · p 0.42 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: AMY2A
Protein: p.Val104Asp
Coding: c.311T>A
MANE Select: NM_000699
Type: single nucleotide variant
Location: chr1:103618096 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 96.68 · 51 PDB
Residue 104: a disulfide bond

Full AMY2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMY2A p.Asn120= Likely benign ★★ same type
AMY2A p.Asn370= Benign/Likely benign ★★ same type
AMY2A p.Thr99Asn Benign ★★ same type
AMY2A p.Ala112Asp Uncertain significance ★ ⚠ same type
AMY2A p.Ala121Thr Uncertain significance ★ ⚠ same type
AMY2A p.Ala124Gly Uncertain significance ★ ⚠ same type
AMY2A p.Ala65Thr Uncertain significance ★ ⚠ same type
AMY2A p.Arg107Cys 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/amy2a-p-val104asp (accessed [today's date]).

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