Is ROGDI p.Asp147= (c.441C>T) pathogenic?

ROGDI p.Asp147= (c.441C>T) is classified Likely benign in ROGDI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-26). Ultra-rare (popmax 0.0135%, amr); Associated with amelocerebrohypohidrotic syndrome.

What condition is associated with ROGDI p.Asp147= (c.441C>T)?

ROGDI p.Asp147= (c.441C>T) is associated with amelocerebrohypohidrotic syndrome (ClinVar).

How common is ROGDI p.Asp147= (c.441C>T) in the general population?

ROGDI p.Asp147= (c.441C>T) is ultra-rare (popmax 0.0135%, amr) (gnomAD).

ROGDI p.Asp147=

c.441C>T · rs777109541 · VCV461612

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, amr)

Conditions

amelocerebrohypohidrotic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5.5	GERP -2.2
Overall
CADD	0.652	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0135% Admixed American · 7/52,036 alleles

Filtering AF 0.00627% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00448%

Overall 0.00121% 19/1,565,226 alleles · ultra-rare exomes 15/1,413,028 · genomes 4/152,198 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0135%	7,434
African / African-American	0.00403%	24,842
Remaining individualsnot grpmax-eligible	0.00328%	30,474
East Asian	0.0023%	43,492
South Asian	0.00117%	85,382
European (non-Finnish)	0.000432%	231,629

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.Asp147=
Coding: c.441C>T
MANE Select: NM_024589
dbSNP: rs777109541
Type: single nucleotide variant
Location: chr16:4798659 (GRCh38)
Gene constraint: LOEUF 1.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.59 · 2 PDB
Residue 147: 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-asp147 (accessed [today's date]).

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