Is GPHN p.Asp75= (c.225T>C) pathogenic?

GPHN p.Asp75= (c.225T>C) is classified Likely benign in GPHN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). Ultra-rare (popmax 0.0166%, mid); Associated with sulfite oxidase deficiency due to molybdenum cofactor deficiency type C.

What condition is associated with GPHN p.Asp75= (c.225T>C)?

GPHN p.Asp75= (c.225T>C) is associated with sulfite oxidase deficiency due to molybdenum cofactor deficiency type C (ClinVar).

How common is GPHN p.Asp75= (c.225T>C) in the general population?

GPHN p.Asp75= (c.225T>C) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

GPHN p.Asp75=

c.225T>C · rs768963547 · VCV1564429

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Conditions

sulfite oxidase deficiency due to molybdenum cofactor deficiency type C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 1.9, phastCons 1
Overall
CADD	12.48	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,036 alleles

Filtering AF 0.00532% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00383%

Overall 0.000754% 12/1,590,888 alleles · ultra-rare exomes 8/1,438,698 · genomes 4/152,190 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,036
African / African-American	0.0108%	9,285
Remaining individualsnot grpmax-eligible	0.00324%	30,824
South Asian	0.0011%	90,540

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: GPHN
Protein: p.Asp75=
Coding: c.225T>C
MANE Select: NM_020806
dbSNP: rs768963547
Type: single nucleotide variant
Location: chr14:66824497 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 84.15 · 1 PDB
Residue 75: the 'mpt mo-transferase' region; an α-helix

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

Disease context

sulfite oxidase deficiency due to molybdenum cofactor deficiency type C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RDH12 p.Lys75Arg Uncertain significance ★ ⚠ same residue
RDH12 p.Lys75Asn Uncertain significance ★ ⚠ same residue
GPHN c.828+1G>A Likely pathogenic ★★ same condition
GPHN p.Tyr56Ter Pathogenic/Likely pathogenic ★★ same condition
GPHN c.1413+3A>G Uncertain significance ★★ same condition
GPHN p.Ala239Thr Uncertain significance ★★ ⚠ same condition
GPHN p.Ala448Ser Uncertain significance ★★ ⚠ same condition
GPHN p.Ala55Ser Uncertain significance ★★ ⚠ 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/gphn-p-asp75 (accessed [today's date]).

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