Is PREP p.Val313Met (c.937G>A) pathogenic?

PREP p.Val313Met (c.937G>A) is classified Uncertain significance in PREP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-04). AlphaMissense: ambiguous (0.4843); Ultra-rare (popmax 0.0236%, nfe).

How common is PREP p.Val313Met (c.937G>A) in the general population?

PREP p.Val313Met (c.937G>A) is ultra-rare (popmax 0.0236%, nfe) (gnomAD).

What do computational predictors say about PREP p.Val313Met (c.937G>A)?

AlphaMissense predicts ambiguous (score 0.4843) — an in-silico prediction, not a clinical call.

PREP p.Val313Met

c.937G>A · rs144257084 · VCV2364791

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4843 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0236%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4843	ambiguous
REVEL	0.224	benign-leaning
SaProt	LLR -9.53	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -0.25, phastCons 1
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0236% European (non-Finnish) · 278/1,180,014 alleles

Filtering AF 0.0213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0204%

Overall 0.0183% 296/1,614,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0236%	4,245
Remaining individualsnot grpmax-eligible	0.008%	12,496
African / African-American	0.00667%	14,985
Admixed American	0.005%	20,000
Finnishnot grpmax-eligible	0.00468%	21,346
East Asian	0.00223%	44,892
South Asian	0.0011%	91,092

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: PREP
Protein: p.Val313Met
Coding: c.937G>A
MANE Select: NM_014889 · reported on NM_002726
dbSNP: rs144257084
Type: single nucleotide variant
Location: chr6:105333392 (GRCh38)
Structure: AlphaFold pLDDT 94.44 · 8 PDB
Residue 313: a disulfide bond; a β-strand

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

Similar variants

PITRM1 p.Cys313Phe Uncertain significance ★ ⚠ same residue
PITRM1 p.Thr931Met Pathogenic/Likely pathogenic ★★ ⚠ same type
PITRM1 p.Ala1003Thr Uncertain significance ★★ ⚠ same type
PITRM1 p.Ala559Val Uncertain significance ★★ ⚠ same type
PITRM1 p.Ala887Val Uncertain significance ★★ ⚠ same type
PITRM1 p.Ala942Val Uncertain significance ★★ ⚠ same type
PITRM1 p.Ala965Thr Uncertain significance ★★ ⚠ same type
PITRM1 p.Arg32Trp 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/prep-p-val313met (accessed [today's date]).

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