Is ADM2 p.Arg87His (c.260G>A) pathogenic?

ADM2 p.Arg87His (c.260G>A) is classified Uncertain significance in ADM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely benign (0.0745); Very rare (popmax 0.00224%, eas).

How common is ADM2 p.Arg87His (c.260G>A) in the general population?

ADM2 p.Arg87His (c.260G>A) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about ADM2 p.Arg87His (c.260G>A)?

AlphaMissense predicts likely benign (score 0.0745) — an in-silico prediction, not a clinical call.

ADM2 p.Arg87His

c.260G>A · rs760679453 · VCV2614444

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0745 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0745	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -7.37	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 0.061	GERP -0.13
Regional constraint	o/e 1.12	unconstrained · MANE · 1,052 bp · p 0.088 · regional, not allelic
Overall
CADD	9.841	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 0.00224% East Asian · 1/44,640 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000436% 7/1,604,208 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,640
Finnishnot grpmax-eligible	0.00163%	61,250
South Asian	0.00111%	90,436
European (non-Finnish)	0.00034%	293,874

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: ADM2
Protein: p.Arg87His
Coding: c.260G>A
MANE Select: NM_001253845
dbSNP: rs760679453
Type: single nucleotide variant
Location: chr22:50482716 (GRCh38)
Gene constraint: LOEUF 1.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.44 · 2 PDB
Residue 87: the 'disordered' region

Full ADM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADM2 p.Arg83= Benign ★★ same type
ADM2 p.Ala54Thr Uncertain significance ★ ⚠ same type
ADM2 p.Ala75Val Uncertain significance ★ ⚠ same type
ADM2 p.Arg107Gly Uncertain significance ★ ⚠ same type
ADM2 p.Arg133Gln Uncertain significance ★ ⚠ same type
ADM2 p.Arg42Trp Uncertain significance ★ ⚠ same type
ADM2 p.Arg56Gln Uncertain significance ★ ⚠ same type
ADM2 p.Arg93Pro 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/adm2-p-arg87his (accessed [today's date]).

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