Is PRSS56 p.Ser48= (c.144C>T) pathogenic?

PRSS56 p.Ser48= (c.144C>T) is classified Likely benign in PRSS56 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-01). Rare (popmax 0.15%, mid); Associated with isolated microphthalmia 6.

What condition is associated with PRSS56 p.Ser48= (c.144C>T)?

PRSS56 p.Ser48= (c.144C>T) is associated with isolated microphthalmia 6 (ClinVar).

How common is PRSS56 p.Ser48= (c.144C>T) in the general population?

PRSS56 p.Ser48= (c.144C>T) is rare (popmax 0.15%, mid) (gnomAD).

PRSS56 p.Ser48=

c.144C>T · rs751017393 · VCV2847751

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.15%, mid)

Conditions

isolated microphthalmia 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -10	GERP -2.9
Overall
CADD	7.921	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.15% Middle Eastern · 9/5,988 alleles

Filtering AF 0.0783% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0585%

Overall 0.00898% 138/1,536,136 alleles · rare exomes 127/1,383,788 · genomes 11/152,348 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.15%	665
Admixed American	0.051%	1,962
Ashkenazi Jewishnot grpmax-eligible	0.0454%	2,204
Remaining individualsnot grpmax-eligible	0.02%	5,001
European (non-Finnish)	0.00645%	15,499
African / African-American	0.00273%	36,593
South Asian	0.00238%	42,032

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: PRSS56
Protein: p.Ser48=
Coding: c.144C>T
MANE Select: NM_001195129
dbSNP: rs751017393
Type: single nucleotide variant
Location: chr2:232521367 (GRCh38)
Gene constraint: LOEUF 1.11 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.35

Full PRSS56 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

isolated microphthalmia 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRSS56 p.Ser48Arg Uncertain significance ★ ⚠ same residue
PRSS56 p.Ala502Thr Uncertain significance ★★ ⚠ same condition
PRSS56 p.Ala57Val Uncertain significance ★★ ⚠ same condition
PRSS56 p.Ala600Thr Uncertain significance ★★ ⚠ same condition
PRSS56 p.Arg247Cys Uncertain significance ★★ ⚠ same condition
PRSS56 p.Asp254Asn Uncertain significance ★★ ⚠ same condition
PRSS56 p.Gly538Ser Uncertain significance ★★ ⚠ same condition
PRSS56 p.Leu483Phe 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/prss56-p-ser48 (accessed [today's date]).

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