Is ADPRM p.Arg16Cys (c.46C>T) pathogenic?

ADPRM p.Arg16Cys (c.46C>T) is classified Uncertain significance in ADPRM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.0729); Ultra-rare (popmax 0.06%, amr).

How common is ADPRM p.Arg16Cys (c.46C>T) in the general population?

ADPRM p.Arg16Cys (c.46C>T) is ultra-rare (popmax 0.06%, amr) (gnomAD).

What do computational predictors say about ADPRM p.Arg16Cys (c.46C>T)?

AlphaMissense predicts likely benign (score 0.0729) — an in-silico prediction, not a clinical call.

ADPRM p.Arg16Cys

c.46C>T · rs370126868 · VCV2456511

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0729 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.06%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0729	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -5.49	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 -0.34	GERP -3.7
Regional constraint	o/e 0.82	unconstrained · MANE · 6,214 bp · p 0.00019 · regional, not allelic
Overall
CADD	8.772	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 0.06% Admixed American · 36/59,954 alleles

Filtering AF 0.0445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0392%

Overall 0.00254% 41/1,613,774 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.06%	1,665
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,580
South Asian	0.0011%	91,060
European (non-Finnish)	0.000254%	393,315

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.Arg16Cys
Coding: c.46C>T
MANE Select: NM_020233
dbSNP: rs370126868
Type: single nucleotide variant
Location: chr17:10704972 (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

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ADPRM p.Arg42Trp Uncertain significance ★ ⚠ same type
ADPRM p.Asn80Lys Uncertain significance ★ ⚠ same type
ADPRM p.Asp74Glu Uncertain significance ★ ⚠ same type
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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-arg16cys (accessed [today's date]).

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