Is PLOD2 p.Arg473Ter (c.1417C>T) pathogenic?

PLOD2 p.Arg473Ter (c.1417C>T) is classified Pathogenic in PLOD2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-07-23). Very rare (popmax 0.0044%, sas).

How common is PLOD2 p.Arg473Ter (c.1417C>T) in the general population?

PLOD2 p.Arg473Ter (c.1417C>T) is very rare (popmax 0.0044%, sas) (gnomAD).

PLOD2 p.Arg473Ter

c.1417C>T · rs750664256 · VCV632404

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 0.39, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0044% South Asian · 4/90,986 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.00124% 20/1,610,074 alleles · very rare exomes 18/1,458,180 · genomes 2/151,894 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0044%	22,747
European (non-Finnish)	0.00136%	73,542

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.Arg473Ter
Coding: c.1417C>T
MANE Select: NM_182943
dbSNP: rs750664256
Type: single nucleotide variant
Location: chr3:146079199 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.63
Residue 473: a UniProt-annotated variant site (in brks2; likely pathogenic); a UniProt-annotated variant site (found in a patient with congenital hydrocephalus; uncertain significance)

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

Similar variants

PLOD2 p.Arg473Gln Uncertain significance ★ ⚠ same residue
PLOD2 c.1500+1G>T Pathogenic/Likely pathogenic ★★ same type
PLOD2 p.Arg440Ter Pathogenic/Likely 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-arg473ter (accessed [today's date]).

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