Is PLOD2 p.Arg479Ser (c.1437G>T) pathogenic?

PLOD2 p.Arg479Ser (c.1437G>T) is classified Uncertain significance in PLOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-31). AlphaMissense: ambiguous (0.4634); Very rare (popmax 0.00017%, nfe).

How common is PLOD2 p.Arg479Ser (c.1437G>T) in the general population?

PLOD2 p.Arg479Ser (c.1437G>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about PLOD2 p.Arg479Ser (c.1437G>T)?

AlphaMissense predicts ambiguous (score 0.4634) — an in-silico prediction, not a clinical call.

PLOD2 p.Arg479Ser

c.1437G>T · rs1187428023 · VCV1802070

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4634 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4634	ambiguous
REVEL	0.579	indeterminate
SaProt	LLR -4.43	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.017	GERP -1.8, phastCons 0.8
Regional constraint	o/e 0.99	unconstrained · MANE · 90 kb · p 0.85 · regional, not allelic
Overall
CADD	21.4	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 0.00017% European (non-Finnish) · 2/1,178,260 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,611,926 alleles · very rare exomes 1/1,459,978 · genomes 1/151,948 · joint denominator

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.Arg479Ser
Coding: c.1437G>T
MANE Select: NM_182943
dbSNP: rs1187428023
Type: single nucleotide variant
Location: chr3:146079179 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.63
Residue 479: a UniProt-annotated variant site (in brks2; likely pathogenic)

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

Similar variants

PLOD2 c.1500+1G>T Pathogenic/Likely pathogenic ★★ same type
PLOD2 p.Arg440Ter Pathogenic/Likely pathogenic ★★ same type
PLOD2 p.Arg473Ter Pathogenic ★★ same type
PLOD2 p.Arg495Ter Pathogenic/Likely pathogenic ★★ same type
PLOD2 p.Arg680Ter Pathogenic/Likely pathogenic ★★ same type
PLOD2 c.1232+5T>A Uncertain significance ★★ same type
PLOD2 c.-170C>G Uncertain significance ★★ same type
PLOD2 p.Ala415Val 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/plod2-p-arg479ser (accessed [today's date]).

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