Is AMY2B p.Arg413His (c.1238G>A) pathogenic?

AMY2B p.Arg413His (c.1238G>A) is classified Uncertain significance in AMY2B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-06). AlphaMissense: likely benign (0.3304); Very rare (popmax 0.00446%, eas).

How common is AMY2B p.Arg413His (c.1238G>A) in the general population?

AMY2B p.Arg413His (c.1238G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about AMY2B p.Arg413His (c.1238G>A)?

AlphaMissense predicts likely benign (score 0.3304) — an in-silico prediction, not a clinical call.

AMY2B p.Arg413His

c.1238G>A · rs749967894 · VCV2389276

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3304 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3304	likely benign
REVEL	0.535	indeterminate
SaProt	LLR -11.11	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 7.4	GERP 0.59, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 7,894 bp · p 0.74 · regional, not allelic
Overall
CADD	29.4	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 0.00446% East Asian · 2/44,872 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00217% 35/1,610,978 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,436
European (non-Finnish)	0.00254%	39,326
South Asian	0.0022%	45,489
African / African-American	0.00134%	74,832

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.Arg413His
Coding: c.1238G>A
MANE Select: NM_001387437
dbSNP: rs749967894
Type: single nucleotide variant
Location: chr1:103577737 (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.Arg413Cys Uncertain significance ★ ⚠ same residue
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

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-arg413his (accessed [today's date]).

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