Is ROGDI p.Asp86Val (c.257A>T) pathogenic?

ROGDI p.Asp86Val (c.257A>T) is classified Uncertain significance in ROGDI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-17). AlphaMissense: likely pathogenic (0.6393); Very rare (popmax 0.00118%, sas); Associated with amelocerebrohypohidrotic syndrome.

What condition is associated with ROGDI p.Asp86Val (c.257A>T)?

ROGDI p.Asp86Val (c.257A>T) is associated with amelocerebrohypohidrotic syndrome (ClinVar).

How common is ROGDI p.Asp86Val (c.257A>T) in the general population?

ROGDI p.Asp86Val (c.257A>T) is very rare (popmax 0.00118%, sas) (gnomAD).

What do computational predictors say about ROGDI p.Asp86Val (c.257A>T)?

AlphaMissense predicts likely pathogenic (score 0.6393) — an in-silico prediction, not a clinical call.

ROGDI p.Asp86Val

c.257A>T · rs774073956 · VCV1447275

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6393 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00118%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

amelocerebrohypohidrotic syndrome

Computational evidence

Protein change
AlphaMissense	0.6393	likely pathogenic
REVEL	0.4	indeterminate
SaProt	LLR -8.80	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.2, phastCons 1
Regional constraint	o/e 1.35	unconstrained · MANE · 5,108 bp · p 7.6e-12 · regional, not allelic
Overall
CADD	25.1	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 0.00118% South Asian · 1/85,084 alleles

Overall 6.39e-05% 1/1,564,660 alleles · very rare exomes 1/1,412,416 · genomes 0/152,244 · 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.Asp86Val
Coding: c.257A>T
MANE Select: NM_024589
dbSNP: rs774073956
Type: single nucleotide variant
Location: chr16:4800577 (GRCh38)
Gene constraint: LOEUF 1.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.59 · 2 PDB
Residue 86: a β-strand

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-asp86val (accessed [today's date]).

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