Is ROGDI p.Arg155Ser (c.465A>C) pathogenic?

ROGDI p.Arg155Ser (c.465A>C) is classified Uncertain significance in ROGDI (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-01). AlphaMissense: likely pathogenic (0.9823); Very rare (popmax 8.59e-05%, nfe); Associated with amelocerebrohypohidrotic syndrome.

What condition is associated with ROGDI p.Arg155Ser (c.465A>C)?

ROGDI p.Arg155Ser (c.465A>C) is associated with amelocerebrohypohidrotic syndrome (ClinVar).

How common is ROGDI p.Arg155Ser (c.465A>C) in the general population?

ROGDI p.Arg155Ser (c.465A>C) is very rare (popmax 8.59e-05%, nfe) (gnomAD).

What do computational predictors say about ROGDI p.Arg155Ser (c.465A>C)?

AlphaMissense predicts likely pathogenic (score 0.9823) — an in-silico prediction, not a clinical call.

ROGDI p.Arg155Ser

c.465A>C · rs1367837038 · VCV1010826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.59e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

amelocerebrohypohidrotic syndrome

Computational evidence

Protein change
AlphaMissense	0.9823	likely pathogenic · top 8% in ROGDI
REVEL	0.346	indeterminate
SaProt	LLR -3.00	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 1, phastCons 1
Regional constraint	o/e 1.35	unconstrained · MANE · 5,108 bp · p 7.6e-12 · regional, not allelic
Overall
CADD	23.3	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 8.59e-05% European (non-Finnish) · 1/1,163,662 alleles

Overall 6.35e-05% 1/1,573,828 alleles · very rare exomes 1/1,421,528 · genomes 0/152,300 · joint denominator

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.Arg155Ser
Coding: c.465A>C
MANE Select: NM_024589
dbSNP: rs1367837038
Type: single nucleotide variant
Location: chr16:4798635 (GRCh38)
Gene constraint: LOEUF 1.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.59 · 2 PDB
Residue 155: an α-helix; a UniProt-annotated variant site (in ktzs; uncertain significance)

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

Disease context

amelocerebrohypohidrotic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
ROGDI p.Gln114Ter Pathogenic/Likely pathogenic ★★ same condition
ROGDI p.Gln96Ter 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-arg155ser (accessed [today's date]).

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