Is PLOD2 p.Pro270Ser (c.808C>T) pathogenic?

PLOD2 p.Pro270Ser (c.808C>T) is classified Uncertain significance in PLOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-16). AlphaMissense: likely pathogenic (0.7259); Very rare (popmax 0.0018%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PLOD2 p.Pro270Ser (c.808C>T)?

PLOD2 p.Pro270Ser (c.808C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PLOD2 p.Pro270Ser (c.808C>T) in the general population?

PLOD2 p.Pro270Ser (c.808C>T) is very rare (popmax 0.0018%, nfe) (gnomAD).

What do computational predictors say about PLOD2 p.Pro270Ser (c.808C>T)?

AlphaMissense predicts likely pathogenic (score 0.7259) — an in-silico prediction, not a clinical call.

PLOD2 p.Pro270Ser

c.808C>T · VCV3307809

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7259 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0018%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7259	likely pathogenic
REVEL	0.631	indeterminate
SaProt	LLR -9.13	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 90 kb · p 0.85 · regional, not allelic
Overall
CADD	26.9	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 0.0018% European (non-Finnish) · 21/1,169,034 alleles

Filtering AF 0.00115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00098%

Overall 0.00137% 22/1,601,592 alleles · very rare exomes 21/1,449,674 · genomes 1/151,918 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0018%	55,668
African / African-American	0.00134%	74,612

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.Pro270Ser
Coding: c.808C>T
MANE Select: NM_182943
Type: single nucleotide variant
Location: chr3:146091871 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.63
Residue 270: 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.Pro270Leu 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-pro270ser (accessed [today's date]).

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