Is UBIAD1 p.Ser75Phe (c.224C>T) pathogenic?

UBIAD1 p.Ser75Phe (c.224C>T) is classified Benign in UBIAD1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-24). AlphaMissense: likely benign (0.1814); Low-frequency (popmax 1.25%, nfe); Associated with Schnyder corneal dystrophy.

What condition is associated with UBIAD1 p.Ser75Phe (c.224C>T)?

UBIAD1 p.Ser75Phe (c.224C>T) is associated with Schnyder corneal dystrophy (ClinVar).

How common is UBIAD1 p.Ser75Phe (c.224C>T) in the general population?

UBIAD1 p.Ser75Phe (c.224C>T) is low-frequency (popmax 1.25%, nfe) (gnomAD).

How is Schnyder corneal dystrophy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about UBIAD1 p.Ser75Phe (c.224C>T)?

AlphaMissense predicts likely benign (score 0.1814) — an in-silico prediction, not a clinical call.

UBIAD1 p.Ser75Phe

c.224C>T · rs114000606 · VCV291821

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1814 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.25%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Schnyder corneal dystrophy

Computational evidence

Protein change
AlphaMissense	0.1814	likely benign
REVEL	0.272	benign-leaning
SaProt	LLR -3.93	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 0.78	GERP 0.53, phastCons 0.073
Regional constraint	o/e 0.49	unconstrained · MANE · 245 bp · p 3.6e-07 · regional, not allelic
Overall
CADD	16.62	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.25% European (non-Finnish) · 14,783/1,180,032 alleles

Filtering AF 1.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.23%

Overall 1.04% 16,715/1,614,146 alleles · low-frequency exomes 15,503/1,461,834 · genomes 1,212/152,312 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.25%	80
Remaining individualsnot grpmax-eligible	1.1%	91
Ashkenazi Jewishnot grpmax-eligible	0.986%	101
Admixed American	0.875%	114
Middle Eastern	0.792%	126
Amishnot grpmax-eligible	0.658%	152
African / African-American	0.238%	419
Finnishnot grpmax-eligible	0.2%	500
South Asian	0.0681%	1,469
East Asian	0.00446%	22,442

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: UBIAD1
Protein: p.Ser75Phe
Coding: c.224C>T
MANE Select: NM_013319
dbSNP: rs114000606
Type: single nucleotide variant
Location: chr1:11273755 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.21
Residue 75: a UniProt-annotated variant site (in)

Full UBIAD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Schnyder corneal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Schnyder corneal dystrophy (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

UBIAD1 p.Gly177Glu Pathogenic/Likely pathogenic ★★ same condition
UBIAD1 p.Leu251Ile Uncertain significance ★★ ⚠ same condition
UBIAD1 p.Pro64Leu Uncertain significance ★★ ⚠ same condition
UBIAD1 c.-47T>G Benign ★★ same condition
UBIAD1 c.*1060G>A Benign ★★ same condition
UBIAD1 c.*1304C>T Benign ★★ same condition
UBIAD1 c.*148A>G Benign ★★ same condition
UBIAD1 c.*904T>C Benign ★★ 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/ubiad1-p-ser75phe (accessed [today's date]).

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