Is ROGDI p.Phe102Ser (c.305T>C) pathogenic?

ROGDI p.Phe102Ser (c.305T>C) is classified Uncertain significance in ROGDI (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-16). AlphaMissense: likely pathogenic (0.9898); No allele count reported in gnomAD v4.1 (AN 1,563,178); Associated with amelocerebrohypohidrotic syndrome.

What condition is associated with ROGDI p.Phe102Ser (c.305T>C)?

ROGDI p.Phe102Ser (c.305T>C) is associated with amelocerebrohypohidrotic syndrome (ClinVar).

How common is ROGDI p.Phe102Ser (c.305T>C) in the general population?

ROGDI p.Phe102Ser (c.305T>C) is no allele count reported in gnomAD v4.1 (AN 1,563,178) (gnomAD).

What do computational predictors say about ROGDI p.Phe102Ser (c.305T>C)?

AlphaMissense predicts likely pathogenic (score 0.9898) — an in-silico prediction, not a clinical call.

ROGDI p.Phe102Ser

c.305T>C · rs2141910617 · VCV1489436

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9898 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,563,178)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

amelocerebrohypohidrotic syndrome

Computational evidence

Protein change
AlphaMissense	0.9898	likely pathogenic · top 6% in ROGDI
REVEL	0.429	indeterminate
SaProt	LLR -9.09	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 11	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	28.4	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

No allele count reported in gnomAD v4.1 (AN 1,563,178). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ROGDI
Protein: p.Phe102Ser
Coding: c.305T>C
MANE Select: NM_024589
dbSNP: rs2141910617
Type: single nucleotide variant
Location: chr16:4800529 (GRCh38)
Gene constraint: LOEUF 1.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.59 · 2 PDB
Residue 102: 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 p.Phe102= 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
ROGDI p.Gln114Ter 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-phe102ser (accessed [today's date]).

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