Is PRSS12 p.Phe65= (c.195C>T) pathogenic?

PRSS12 p.Phe65= (c.195C>T) is classified Uncertain significance in PRSS12 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-27). Very rare (popmax 0.00162%, nfe); Associated with intellectual disability, autosomal recessive 1.

What condition is associated with PRSS12 p.Phe65= (c.195C>T)?

PRSS12 p.Phe65= (c.195C>T) is associated with intellectual disability, autosomal recessive 1 (ClinVar).

How common is PRSS12 p.Phe65= (c.195C>T) in the general population?

PRSS12 p.Phe65= (c.195C>T) is very rare (popmax 0.00162%, nfe) (gnomAD).

PRSS12 p.Phe65=

c.195C>T · rs1671147684 · VCV899734

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00162%, nfe)

Conditions

intellectual disability, autosomal recessive 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.2	GERP 1.1, phastCons 0.99
Overall
CADD	10.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00162% European (non-Finnish) · 18/1,108,386 alleles

Filtering AF 0.00101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000837%

Overall 0.00122% 18/1,474,084 alleles · very rare exomes 18/1,322,362 · genomes 0/151,722 · joint denominator

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: PRSS12
Protein: p.Phe65=
Coding: c.195C>T
MANE Select: NM_003619
dbSNP: rs1671147684
Type: single nucleotide variant
Location: chr4:118352526 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.42
Residue 65: the 'disordered' region

Full PRSS12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, autosomal recessive 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRSS12 c.2320+6G>C Uncertain significance ★★ same condition
PRSS12 c.821-1G>A Uncertain significance ★★ same condition
PRSS12 c.*1615C>T Uncertain significance ★★ same condition
PRSS12 c.*221A>T Uncertain significance ★★ same condition
PRSS12 p.Ala547Asp Uncertain significance ★★ ⚠ same condition
PRSS12 p.Ala79Pro Uncertain significance ★★ ⚠ same condition
PRSS12 p.Arg292Trp Uncertain significance ★★ ⚠ same condition
PRSS12 p.Arg426Gln 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/prss12-p-phe65 (accessed [today's date]).

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