Is PLOD2 p.Val298Leu (c.892G>C) pathogenic?

PLOD2 p.Val298Leu (c.892G>C) is classified Uncertain significance in PLOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-26). AlphaMissense: ambiguous (0.452); Very rare (popmax 8.52e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PLOD2 p.Val298Leu (c.892G>C)?

PLOD2 p.Val298Leu (c.892G>C) is associated with Inborn genetic diseases (ClinVar).

How common is PLOD2 p.Val298Leu (c.892G>C) in the general population?

PLOD2 p.Val298Leu (c.892G>C) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

What do computational predictors say about PLOD2 p.Val298Leu (c.892G>C)?

AlphaMissense predicts ambiguous (score 0.452) — an in-silico prediction, not a clinical call.

PLOD2 p.Val298Leu

c.892G>C · rs947167279 · VCV2273381

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.452 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.452	ambiguous
REVEL	0.743	pathogenic-leaning
SaProt	LLR -12.59	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.37	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 4	GERP 2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 90 kb · p 0.85 · regional, not allelic
Overall
CADD	28.9	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 8.52e-05% European (non-Finnish) · 1/1,173,940 alleles

Overall 6.87e-05% 1/1,455,026 alleles · very rare

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: PLOD2
Protein: p.Val298Leu
Coding: c.892G>C
MANE Select: NM_182943
dbSNP: rs947167279
Type: single nucleotide variant
Location: chr3:146088699 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.63
Residue 298: a UniProt-annotated variant site (in brks2; likely pathogenic)

Full PLOD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLOD2 p.Val298Ile Uncertain significance ★★ ⚠ same residue
PLOD2 p.Arg205Met Uncertain significance ★★ ⚠ same condition
PLOD2 p.Arg495Gln Uncertain significance ★★ ⚠ same condition
PLOD2 p.Asn255Ile Uncertain significance ★★ ⚠ same condition
PLOD2 p.Asp293Asn Uncertain significance ★★ ⚠ same condition
PLOD2 p.Asp316Gly Uncertain significance ★★ ⚠ same condition
PLOD2 p.Asp348Tyr Uncertain significance ★★ ⚠ same condition
PLOD2 p.Glu112Gly 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/plod2-p-val298leu (accessed [today's date]).

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