Is PRSS12 p.Ser820= (c.2460C>T) pathogenic?

PRSS12 p.Ser820= (c.2460C>T) is classified Uncertain significance in PRSS12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-12). Rare (popmax 0.129%, nfe); Associated with intellectual disability, autosomal recessive 1.

What condition is associated with PRSS12 p.Ser820= (c.2460C>T)?

PRSS12 p.Ser820= (c.2460C>T) is associated with intellectual disability, autosomal recessive 1 (ClinVar).

How common is PRSS12 p.Ser820= (c.2460C>T) in the general population?

PRSS12 p.Ser820= (c.2460C>T) is rare (popmax 0.129%, nfe) (gnomAD).

PRSS12 p.Ser820=

c.2460C>T · rs146650218 · VCV347392

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.129%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 0.1, phastCons 1
Overall
CADD	18.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.129% European (non-Finnish) · 1,523/1,180,036 alleles

Filtering AF 0.124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.121%

Overall 0.104% 1,685/1,614,196 alleles · rare exomes 1,565/1,461,894 · genomes 120/152,302 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.129%	775
South Asian	0.0988%	1,012
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.0544%	1,839
African / African-American	0.0293%	3,411
Finnishnot grpmax-eligible	0.00937%	10,673
Admixed American	0.00833%	12,005

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.Ser820=
Coding: c.2460C>T
MANE Select: NM_003619
dbSNP: rs146650218
Type: single nucleotide variant
Location: chr4:118282104 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.42
Residue 820: the peptidase s1 domain

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 p.Ser820Cys Uncertain significance ★ ⚠ same residue
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

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-ser820 (accessed [today's date]).

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