Is AMY2B p.Asp332Val (c.995A>T) pathogenic?

AMY2B p.Asp332Val (c.995A>T) is classified Uncertain significance in AMY2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-19). AlphaMissense: ambiguous (0.3533); Very rare (popmax 0.000254%, nfe).

How common is AMY2B p.Asp332Val (c.995A>T) in the general population?

AMY2B p.Asp332Val (c.995A>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about AMY2B p.Asp332Val (c.995A>T)?

AlphaMissense predicts ambiguous (score 0.3533) — an in-silico prediction, not a clinical call.

AMY2B p.Asp332Val

c.995A>T · rs2524229723 · VCV3117375

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3533 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3533	ambiguous
REVEL	0.723	pathogenic-leaning
SaProt	LLR -13.21	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.32	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 9.1	GERP 1.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 7,894 bp · p 0.74 · regional, not allelic
Overall
CADD	25.3	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 0.000254% European (non-Finnish) · 3/1,179,668 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,342 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: AMY2B
Protein: p.Asp332Val
Coding: c.995A>T
MANE Select: NM_001387437
dbSNP: rs2524229723
Type: single nucleotide variant
Location: chr1:103575339 (GRCh38)
Gene constraint: LOEUF 1.395 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.70

Full AMY2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMY2B p.Leu31= Benign/Likely benign ★★ same type
AMY2B p.Ala121Thr Uncertain significance ★ ⚠ same type
AMY2B p.Ala15Thr Uncertain significance ★ ⚠ same type
AMY2B p.Ala339Val Uncertain significance ★ ⚠ same type
AMY2B p.Ala40Val Uncertain significance ★ ⚠ same type
AMY2B p.Ala433Thr Uncertain significance ★ ⚠ same type
AMY2B p.Ala490Ser Uncertain significance ★ ⚠ same type
AMY2B p.Ala65Thr 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/amy2b-p-asp332val (accessed [today's date]).

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