Is PRDM5 p.Ser15Phe (c.44C>T) pathogenic?

PRDM5 p.Ser15Phe (c.44C>T) is classified Uncertain significance in PRDM5 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.5933); Very rare (popmax 0.00661%, sas); Associated with brittle cornea syndrome 2.

What condition is associated with PRDM5 p.Ser15Phe (c.44C>T)?

PRDM5 p.Ser15Phe (c.44C>T) is associated with brittle cornea syndrome 2 (ClinVar).

How common is PRDM5 p.Ser15Phe (c.44C>T) in the general population?

PRDM5 p.Ser15Phe (c.44C>T) is very rare (popmax 0.00661%, sas) (gnomAD).

How is Brittle cornea syndrome inherited?

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

What do computational predictors say about PRDM5 p.Ser15Phe (c.44C>T)?

AlphaMissense predicts likely pathogenic (score 0.5933) — an in-silico prediction, not a clinical call.

PRDM5 p.Ser15Phe

c.44C>T · rs759134690 · VCV2585362

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5933 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00661%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

brittle cornea syndrome 2

Computational evidence

Protein change
AlphaMissense	0.5933	likely pathogenic
REVEL	0.433	indeterminate
SaProt	LLR -6.90	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 145 kb · p 0.23 · regional, not allelic
Overall
CADD	29.8	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 0.00661% South Asian · 6/90,830 alleles

Filtering AF 0.00287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00196%

Overall 0.000559% 9/1,610,968 alleles · very rare exomes 8/1,459,082 · genomes 1/151,886 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00661%	15,138
African / African-American	0.00267%	37,399
Remaining individualsnot grpmax-eligible	0.0016%	62,362

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: PRDM5
Protein: p.Ser15Phe
Coding: c.44C>T
MANE Select: NM_018699
dbSNP: rs759134690
Type: single nucleotide variant
Location: chr4:120922565 (GRCh38)
Gene constraint: LOEUF 0.899 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.53 · 1 PDB
Residue 15: the set domain

Full PRDM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

brittle cornea syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Brittle cornea syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

PRDM5 c.1623+1G>A Likely pathogenic ★★ same condition
PRDM5 c.865+1G>A Likely pathogenic ★★ same condition
PRDM5 p.Arg232Ter Pathogenic/Likely pathogenic ★★ same condition
PRDM5 p.Arg346Ter Pathogenic ★★ same condition
PRDM5 p.Gln420Ter Pathogenic/Likely pathogenic ★★ same condition
PRDM5 p.Glu103Ter Pathogenic/Likely pathogenic ★★ same condition
PRDM5 p.Glu344Ter Pathogenic/Likely pathogenic ★★ same condition
PRDM5 c.650+5G>A 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/prdm5-p-ser15phe (accessed [today's date]).

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