Is PRSS56 p.Pro200= (c.600G>A) pathogenic?

PRSS56 p.Pro200= (c.600G>A) is classified Benign/Likely benign in PRSS56 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-08). Rare (popmax 0.583%, afr); Associated with isolated microphthalmia 6.

What condition is associated with PRSS56 p.Pro200= (c.600G>A)?

PRSS56 p.Pro200= (c.600G>A) is associated with isolated microphthalmia 6 (ClinVar).

How common is PRSS56 p.Pro200= (c.600G>A) in the general population?

PRSS56 p.Pro200= (c.600G>A) is rare (popmax 0.583%, afr) (gnomAD).

PRSS56 p.Pro200=

c.600G>A · rs534508338 · VCV767012

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.583%, afr)

Conditions

isolated microphthalmia 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.40	donor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP -13	GERP -3.7
Overall
CADD	0.667	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.583% African / African-American · 425/72,928 alleles

Filtering AF 0.537% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.519%

Overall 0.0301% 461/1,531,796 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.583%	172
Remaining individualsnot grpmax-eligible	0.0318%	3,146
Admixed American	0.0236%	4,230
Middle Eastern	0.0168%	5,968
South Asian	0.00119%	83,726
European (non-Finnish)	0.000262%	381,400

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.Pro200=
Coding: c.600G>A
MANE Select: NM_001195129
dbSNP: rs534508338
Type: single nucleotide variant
Location: chr2:232522755 (GRCh38)
Gene constraint: LOEUF 1.11 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.35
Residue 200: the peptidase s1 domain

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.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
PRSS56 p.Pro354Ala 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-pro200 (accessed [today's date]).

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