Is ADPRM p.His341Arg (c.1022A>G) pathogenic?

ADPRM p.His341Arg (c.1022A>G) is classified Uncertain significance in ADPRM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-09). AlphaMissense: likely benign (0.056); Ultra-rare (popmax 0.0166%, mid).

How common is ADPRM p.His341Arg (c.1022A>G) in the general population?

ADPRM p.His341Arg (c.1022A>G) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about ADPRM p.His341Arg (c.1022A>G)?

AlphaMissense predicts likely benign (score 0.056) — an in-silico prediction, not a clinical call.

ADPRM p.His341Arg

c.1022A>G · VCV3501903

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.056 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.056	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -5.90	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 0.18	GERP -0.66
Regional constraint	o/e 0.82	unconstrained · MANE · 6,214 bp · p 0.00019 · regional, not allelic
Overall
CADD	8.031	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 0.0166% Middle Eastern · 1/6,026 alleles

Filtering AF 0.000362% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000262%

Overall 0.000625% 10/1,600,734 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,026
European (non-Finnish)	0.000769%	130,114

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: ADPRM
Protein: p.His341Arg
Coding: c.1022A>G
MANE Select: NM_020233
Type: single nucleotide variant
Location: chr17:10711137 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.59

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

Similar variants

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ADPRM p.Ala24Val Uncertain significance ★ ⚠ same type
ADPRM p.Arg16Cys Uncertain significance ★ ⚠ same type
ADPRM p.Arg324Lys Uncertain significance ★ ⚠ same type
ADPRM p.Arg42Trp Uncertain significance ★ ⚠ same type
ADPRM p.Asn80Lys Uncertain significance ★ ⚠ same type
ADPRM p.Asp74Glu Uncertain significance ★ ⚠ same type
ADPRM p.Asp77Asn 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/adprm-p-his341arg (accessed [today's date]).

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