Is PLTP p.Ala283Val (c.848C>T) pathogenic?

PLTP p.Ala283Val (c.848C>T) is classified Uncertain significance in PLTP (ClinVar, Single submitter, 2 submitters; last evaluated 2024-01-21). AlphaMissense: likely benign (0.1963); Rare (popmax 0.154%, sas).

How common is PLTP p.Ala283Val (c.848C>T) in the general population?

PLTP p.Ala283Val (c.848C>T) is rare (popmax 0.154%, sas) (gnomAD).

What do computational predictors say about PLTP p.Ala283Val (c.848C>T)?

AlphaMissense predicts likely benign (score 0.1963) — an in-silico prediction, not a clinical call.

PLTP p.Ala283Val

c.848C>T · rs142277281 · VCV3020935

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1963 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.154%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1963	likely benign
REVEL	0.37	indeterminate
SaProt	LLR -8.83	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 13 kb · p 0.099 · regional, not allelic
Overall
CADD	25.9	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

Grpmax group 0.154% South Asian · 140/91,088 alleles

Filtering AF 0.133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.125%

Overall 0.0111% 179/1,614,218 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.154%	651
Remaining individualsnot grpmax-eligible	0.016%	6,251
East Asian	0.0156%	6,413
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
European (non-Finnish)	0.00161%	62,108
African / African-American	0.00133%	75,042

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: PLTP
Protein: p.Ala283Val
Coding: c.848C>T
MANE Select: NM_006227
dbSNP: rs142277281
Type: single nucleotide variant
Location: chr20:45904976 (GRCh38)
Gene constraint: LOEUF 1.002 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.36

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

Similar variants

PLTP p.Ala283Thr Uncertain significance ★ ⚠ same residue
PLTP p.Ala283= Likely benign ★ same residue
PLTP p.Ala155Thr Uncertain significance ★★ ⚠ same type
PLTP p.Ala155Val Uncertain significance ★★ ⚠ same type
PLTP p.Arg177Cys Uncertain significance ★★ ⚠ same type
PLTP p.Arg251Gln Uncertain significance ★★ ⚠ same type
PLTP p.Arg372His Uncertain significance ★★ ⚠ same type
PLTP p.Arg380Gln 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/pltp-p-ala283val (accessed [today's date]).

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