Is GPHN p.Pro371= (c.1113G>A) pathogenic?

GPHN p.Pro371= (c.1113G>A) is classified Likely benign in GPHN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-15). Ultra-rare (popmax 0.0117%, amr); Associated with sulfite oxidase deficiency due to molybdenum cofactor deficiency type C.

What condition is associated with GPHN p.Pro371= (c.1113G>A)?

GPHN p.Pro371= (c.1113G>A) is associated with sulfite oxidase deficiency due to molybdenum cofactor deficiency type C (ClinVar).

How common is GPHN p.Pro371= (c.1113G>A) in the general population?

GPHN p.Pro371= (c.1113G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

GPHN p.Pro371=

c.1113G>A · rs770812117 · VCV1116464

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

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 3.1	GERP 1.9, phastCons 1
Overall
CADD	14.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,992 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00136% 22/1,613,444 alleles · ultra-rare exomes 19/1,461,356 · genomes 3/152,088 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,570
East Asian	0.00446%	22,445
South Asian	0.00439%	22,766
Finnishnot grpmax-eligible	0.00156%	63,988
European (non-Finnish)	0.000678%	147,443

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.Pro371=
Coding: c.1113G>A
MANE Select: NM_020806
dbSNP: rs770812117
Type: single nucleotide variant
Location: chr14:67058755 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 84.15 · 1 PDB
Residue 371: 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.Pro371Leu Uncertain significance ★ ⚠ same residue
GPHN p.Pro371Ser 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-pro371 (accessed [today's date]).

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