Is PLOD2 p.Val41Ile (c.121G>A) pathogenic?

PLOD2 p.Val41Ile (c.121G>A) is classified Uncertain significance in PLOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.0898); No allele count reported in gnomAD v4.1 (AN 1,571,734); Associated with Bruck syndrome 2.

What condition is associated with PLOD2 p.Val41Ile (c.121G>A)?

PLOD2 p.Val41Ile (c.121G>A) is associated with Bruck syndrome 2 (ClinVar).

How common is PLOD2 p.Val41Ile (c.121G>A) in the general population?

PLOD2 p.Val41Ile (c.121G>A) is no allele count reported in gnomAD v4.1 (AN 1,571,734) (gnomAD).

What do computational predictors say about PLOD2 p.Val41Ile (c.121G>A)?

AlphaMissense predicts likely benign (score 0.0898) — an in-silico prediction, not a clinical call.

PLOD2 p.Val41Ile

c.121G>A · rs2030399859 · VCV902771

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0898 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,571,734)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bruck syndrome 2

Computational evidence

Protein change
AlphaMissense	0.0898	likely benign
REVEL	0.165	moderately benign-leaning
SaProt	LLR -4.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 90 kb · p 0.85 · regional, not allelic
Overall
CADD	24.8	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

No allele count reported in gnomAD v4.1 (AN 1,571,734). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PLOD2
Protein: p.Val41Ile
Coding: c.121G>A
MANE Select: NM_182943
dbSNP: rs2030399859
Type: single nucleotide variant
Location: chr3:146124218 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.63

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

Disease context

Bruck syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLOD2 p.Arg440Ter Pathogenic/Likely pathogenic ★★ same condition
PLOD2 p.Arg495Ter Pathogenic/Likely pathogenic ★★ same condition
PLOD2 p.Arg680Ter Pathogenic/Likely pathogenic ★★ same condition
PLOD2 c.-170C>G Uncertain significance ★★ same condition
PLOD2 p.Ala415Val Uncertain significance ★★ ⚠ same condition
PLOD2 p.Arg619Cys Uncertain significance ★★ ⚠ same condition
PLOD2 p.Arg648Trp Uncertain significance ★★ ⚠ same condition
PLOD2 p.Asp102Glu 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-val41ile (accessed [today's date]).

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