Is PRSS8 p.Val6Phe (c.16G>T) pathogenic?

PRSS8 p.Val6Phe (c.16G>T) is classified Uncertain significance in PRSS8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-02). AlphaMissense: likely benign (0.0572); Ultra-rare (popmax 0.0315%, sas).

How common is PRSS8 p.Val6Phe (c.16G>T) in the general population?

PRSS8 p.Val6Phe (c.16G>T) is ultra-rare (popmax 0.0315%, sas) (gnomAD).

What do computational predictors say about PRSS8 p.Val6Phe (c.16G>T)?

AlphaMissense predicts likely benign (score 0.0572) — an in-silico prediction, not a clinical call.

PRSS8 p.Val6Phe

c.16G>T · VCV3310749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0572 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0315%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0572	likely benign
REVEL	0.363	indeterminate
SaProt	LLR -6.92	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -1.8, phastCons 0.07
Regional constraint	o/e 0.82	unconstrained · MANE · 3,486 bp · p 0.00011 · regional, not allelic
Overall
CADD	14.46	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0315% South Asian · 27/85,842 alleles

Filtering AF 0.0222% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.019%

Overall 0.00178% 28/1,573,400 alleles · ultra-rare exomes 28/1,421,084 · genomes 0/152,316 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0315%	3,179
Remaining individualsnot grpmax-eligible	0.00164%	60,990

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: PRSS8
Protein: p.Val6Phe
Coding: c.16G>T
MANE Select: NM_002773
Type: single nucleotide variant
Location: chr16:31135483 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 84.49 · 9 PDB

Full PRSS8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRSS8 p.Gly8Glu Benign ★★ same type
PRSS8 p.Ala160Thr Uncertain significance ★ ⚠ same type
PRSS8 p.Ala233Thr Uncertain significance ★ same type
PRSS8 p.Ala278Pro Uncertain significance ★ ⚠ same type
PRSS8 p.Ala317Gly Uncertain significance ★ ⚠ same type
PRSS8 p.Ala95Val Uncertain significance ★ ⚠ same type
PRSS8 p.Arg44Cys Uncertain significance ★ ⚠ same type
PRSS8 p.Asp237Ala Uncertain significance ★ ⚠ same type

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/prss8-p-val6phe (accessed [today's date]).

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