Is GPHN p.Pro201Ser (c.601C>T) pathogenic?

GPHN p.Pro201Ser (c.601C>T) is classified Uncertain significance in GPHN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-15). AlphaMissense: likely benign (0.0636); Very rare (popmax 0.00834%, amr); Associated with sulfite oxidase deficiency due to molybdenum cofactor deficiency type C.

What condition is associated with GPHN p.Pro201Ser (c.601C>T)?

GPHN p.Pro201Ser (c.601C>T) is associated with sulfite oxidase deficiency due to molybdenum cofactor deficiency type C (ClinVar).

How common is GPHN p.Pro201Ser (c.601C>T) in the general population?

GPHN p.Pro201Ser (c.601C>T) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about GPHN p.Pro201Ser (c.601C>T)?

AlphaMissense predicts likely benign (score 0.0636) — an in-silico prediction, not a clinical call.

GPHN p.Pro201Ser

c.601C>T · rs568241284 · VCV2200821

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0636 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

sulfite oxidase deficiency due to molybdenum cofactor deficiency type C

Computational evidence

Protein change
AlphaMissense	0.0636	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -6.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 136 kb · p 0.021 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,988 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000558% 9/1,613,628 alleles · very rare exomes 4/1,461,500 · genomes 5/152,128 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,998
African / African-American	0.00534%	18,742

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.Pro201Ser
Coding: c.601C>T
MANE Select: NM_020806
dbSNP: rs568241284
Type: single nucleotide variant
Location: chr14:66922810 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 84.15 · 1 PDB
Residue 201: the 'interaction with gabarap' region; the 'disordered' 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.Pro201= Likely benign ★ same residue
RDH12 p.Cys201Arg Pathogenic ★★ same residue
PALS1 p.His201Leu 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

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-pro201ser (accessed [today's date]).

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