Is GPHN p.Arg708= (c.2122C>A) pathogenic?

GPHN p.Arg708= (c.2122C>A) is classified Uncertain significance in GPHN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). No allele count reported in gnomAD v4.1 (AN 1,608,650); Associated with sulfite oxidase deficiency due to molybdenum cofactor deficiency type C.

What condition is associated with GPHN p.Arg708= (c.2122C>A)?

GPHN p.Arg708= (c.2122C>A) is associated with sulfite oxidase deficiency due to molybdenum cofactor deficiency type C (ClinVar).

How common is GPHN p.Arg708= (c.2122C>A) in the general population?

GPHN p.Arg708= (c.2122C>A) is no allele count reported in gnomAD v4.1 (AN 1,608,650) (gnomAD).

GPHN p.Arg708=

c.2122C>A · VCV4721318

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,650)

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
Pangolin	Δ0.34	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.8	GERP 2.1, phastCons 1
Overall
CADD	11.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,608,650). 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: GPHN
Protein: p.Arg708=
Coding: c.2122C>A
MANE Select: NM_020806
Type: single nucleotide variant
Location: chr14:67179620 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 84.15 · 1 PDB
Residue 708: the 'mpt adenylyltransferase' region

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

GPHN p.Arg708Trp Uncertain significance ★★ ⚠ same residue
GPHN p.Arg708Gln 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-arg708 (accessed [today's date]).

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