Is ROGDI p.Arg12Trp (c.34C>T) pathogenic?

ROGDI p.Arg12Trp (c.34C>T) is classified Uncertain significance in ROGDI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-24). AlphaMissense: likely pathogenic (0.9172); Ultra-rare (popmax 0.06%, mid); Associated with Inborn genetic diseases.

What condition is associated with ROGDI p.Arg12Trp (c.34C>T)?

ROGDI p.Arg12Trp (c.34C>T) is associated with Inborn genetic diseases, amelocerebrohypohidrotic syndrome (ClinVar).

How common is ROGDI p.Arg12Trp (c.34C>T) in the general population?

ROGDI p.Arg12Trp (c.34C>T) is ultra-rare (popmax 0.06%, mid) (gnomAD).

What do computational predictors say about ROGDI p.Arg12Trp (c.34C>T)?

AlphaMissense predicts likely pathogenic (score 0.9172) — an in-silico prediction, not a clinical call.

ROGDI p.Arg12Trp

c.34C>T · rs867005426 · VCV937507

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9172 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.06%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9172	likely pathogenic
REVEL	0.268	benign-leaning
SaProt	LLR -10.43	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.4, phastCons 1
Regional constraint	o/e 1.35	unconstrained · MANE · 5,108 bp · p 7.6e-12 · regional, not allelic
Overall
CADD	27.2	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 0.06% Middle Eastern · 2/3,336 alleles

Filtering AF 0.0106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00444%

Overall 0.000865% 11/1,271,976 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.06%	1,668
Admixed American	0.00675%	14,819
Finnishnot grpmax-eligible	0.00302%	33,132
European (non-Finnish)	0.000598%	167,222

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: ROGDI
Protein: p.Arg12Trp
Coding: c.34C>T
MANE Select: NM_024589
dbSNP: rs867005426
Type: single nucleotide variant
Location: chr16:4802538 (GRCh38)
Gene constraint: LOEUF 1.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.59 · 2 PDB
Residue 12: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: amelocerebrohypohidrotic syndrome

Similar variants

ROGDI p.Arg12Leu Uncertain significance ★ ⚠ same residue
ROGDI p.Arg12= Likely benign ★ same residue
ROGDI c.117+1G>A Pathogenic/Likely pathogenic ★★ same condition
ROGDI c.46-2A>G Likely pathogenic ★★ same condition
ROGDI c.531+5G>C Likely pathogenic ★★ same condition
ROGDI c.645+2T>A Likely pathogenic ★★ same condition
ROGDI p.Arg157Ter Pathogenic ★★ same condition
ROGDI p.Gln112Ter Pathogenic/Likely pathogenic ★★ same condition

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/rogdi-p-arg12trp (accessed [today's date]).

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