Is ADPRM p.Arg42Trp (c.124C>T) pathogenic?

ADPRM p.Arg42Trp (c.124C>T) is classified Uncertain significance in ADPRM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-04). AlphaMissense: likely benign (0.1653); Very rare (popmax 0.00534%, afr).

How common is ADPRM p.Arg42Trp (c.124C>T) in the general population?

ADPRM p.Arg42Trp (c.124C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about ADPRM p.Arg42Trp (c.124C>T)?

AlphaMissense predicts likely benign (score 0.1653) — an in-silico prediction, not a clinical call.

ADPRM p.Arg42Trp

c.124C>T · VCV3273635

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1653 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1653	likely benign
REVEL	0.555	indeterminate
SaProt	LLR -12.59	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 2.1	GERP -2.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 6,214 bp · p 0.00019 · regional, not allelic
Overall
CADD	23.2	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 0.00534% African / African-American · 4/74,878 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000867% 14/1,613,932 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,720
European (non-Finnish)	0.000847%	118,001

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.Arg42Trp
Coding: c.124C>T
MANE Select: NM_020233
Type: single nucleotide variant
Location: chr17:10705050 (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

ADPRM p.Ala248Thr Uncertain significance ★ ⚠ same type
ADPRM p.Ala24Val Uncertain significance ★ ⚠ same type
ADPRM p.Arg16Cys Uncertain significance ★ ⚠ same type
ADPRM p.Arg324Lys 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
ADPRM p.Asp95Glu 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-arg42trp (accessed [today's date]).

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