Is GPHN p.Thr139= (c.417G>A) pathogenic?

GPHN p.Thr139= (c.417G>A) is classified Likely benign in GPHN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-17). Very rare (popmax 0.0033%, sas); Associated with sulfite oxidase deficiency due to molybdenum cofactor deficiency type C.

What condition is associated with GPHN p.Thr139= (c.417G>A)?

GPHN p.Thr139= (c.417G>A) is associated with sulfite oxidase deficiency due to molybdenum cofactor deficiency type C (ClinVar).

How common is GPHN p.Thr139= (c.417G>A) in the general population?

GPHN p.Thr139= (c.417G>A) is very rare (popmax 0.0033%, sas) (gnomAD).

GPHN p.Thr139=

c.417G>A · rs763888545 · VCV2973120

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

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 0.34	GERP -2.2, phastCons 1
Overall
CADD	10.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0033% South Asian · 3/90,860 alleles

Filtering AF 0.000877% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000624% 10/1,603,768 alleles · very rare exomes 9/1,451,586 · genomes 1/152,182 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,287
East Asian	0.00223%	44,818
European (non-Finnish)	0.000513%	195,107

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.Thr139=
Coding: c.417G>A
MANE Select: NM_020806
dbSNP: rs763888545
Type: single nucleotide variant
Location: chr14:66916030 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 84.15 · 1 PDB
Residue 139: the 'mpt mo-transferase' region; a β-strand

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.Gly139= Likely benign ★ 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
GPHN p.Ala590Ser 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-thr139 (accessed [today's date]).

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