Is AMY2B p.Arg267Gln (c.800G>A) pathogenic?

AMY2B p.Arg267Gln (c.800G>A) is classified Uncertain significance in AMY2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-19). AlphaMissense: likely benign (0.238); Ultra-rare (popmax 0.012%, afr).

How common is AMY2B p.Arg267Gln (c.800G>A) in the general population?

AMY2B p.Arg267Gln (c.800G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about AMY2B p.Arg267Gln (c.800G>A)?

AlphaMissense predicts likely benign (score 0.238) — an in-silico prediction, not a clinical call.

AMY2B p.Arg267Gln

c.800G>A · rs200275225 · VCV3117366

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.238 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.238	likely benign
REVEL	0.686	pathogenic-leaning
SaProt	LLR -10.87	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.35	GERP 0.56
Regional constraint	o/e 1.01	unconstrained · MANE · 7,894 bp · p 0.74 · regional, not allelic
Overall
CADD	23.4	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 0.012% African / African-American · 9/74,900 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00385% 62/1,611,606 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,322
European (non-Finnish)	0.00398%	25,100
Admixed American	0.00333%	29,986
South Asian	0.0033%	30,323
Remaining individualsnot grpmax-eligible	0.00161%	62,300

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.Arg267Gln
Coding: c.800G>A
MANE Select: NM_001387437
dbSNP: rs200275225
Type: single nucleotide variant
Location: chr1:103574315 (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-arg267gln (accessed [today's date]).

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