Is PRSS56 p.Arg324= (c.972C>A) pathogenic?

PRSS56 p.Arg324= (c.972C>A) is classified Likely benign in PRSS56 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). Rare (popmax 0.104%, afr); Associated with isolated microphthalmia 6.

What condition is associated with PRSS56 p.Arg324= (c.972C>A)?

PRSS56 p.Arg324= (c.972C>A) is associated with isolated microphthalmia 6 (ClinVar).

How common is PRSS56 p.Arg324= (c.972C>A) in the general population?

PRSS56 p.Arg324= (c.972C>A) is rare (popmax 0.104%, afr) (gnomAD).

PRSS56 p.Arg324=

c.972C>A · rs539085160 · VCV733309

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.104%, afr)

Conditions

isolated microphthalmia 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.2	GERP -3.9
Overall
CADD	1.419	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.104% African / African-American · 76/73,094 alleles

Filtering AF 0.0851% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0782%

Overall 0.00515% 79/1,532,634 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.104%	962
Middle Eastern	0.0187%	5,356
Admixed American	0.00198%	50,530
Remaining individualsnot grpmax-eligible	0.00167%	59,822

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.Arg324=
Coding: c.972C>A
MANE Select: NM_001195129
dbSNP: rs539085160
Type: single nucleotide variant
Location: chr2:232523538 (GRCh38)
Gene constraint: LOEUF 1.11 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.35
Residue 324: 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.Arg324Cys Likely pathogenic ★ 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-arg324 (accessed [today's date]).

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