Is PLTP p.Ser124Tyr (c.371C>A) pathogenic?

PLTP p.Ser124Tyr (c.371C>A) is classified Benign in PLTP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-08). AlphaMissense: likely benign (0.1334); Low-frequency (popmax 4.17%, afr).

How common is PLTP p.Ser124Tyr (c.371C>A) in the general population?

PLTP p.Ser124Tyr (c.371C>A) is low-frequency (popmax 4.17%, afr) (gnomAD).

What do computational predictors say about PLTP p.Ser124Tyr (c.371C>A)?

AlphaMissense predicts likely benign (score 0.1334) — an in-silico prediction, not a clinical call.

PLTP p.Ser124Tyr

c.371C>A · rs11569636 · VCV780609

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1334 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.17%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1334	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -8.39	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 3.2	GERP -0.43, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 13 kb · p 0.099 · regional, not allelic
Overall
CADD	18.9	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 4.17% African / African-American · 3,130/75,022 alleles

Filtering AF 4.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 4%

Overall 0.234% 3,782/1,614,142 alleles · low-frequency exomes 2,009/1,461,870 · genomes 1,773/152,272 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.17%	24
Middle Eastern	0.61%	164
Remaining individualsnot grpmax-eligible	0.342%	292
Admixed American	0.295%	339
South Asian	0.114%	876
European (non-Finnish)	0.0102%	9,834

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.Ser124Tyr
Coding: c.371C>A
MANE Select: NM_006227
dbSNP: rs11569636
Type: single nucleotide variant
Location: chr20:45909630 (GRCh38)
Gene constraint: LOEUF 1.002 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.36
Residue 124: a UniProt-annotated variant site (in)

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

Similar variants

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
PLTP p.Arg391Cys Uncertain significance ★★ ⚠ same type
PLTP p.Arg394Pro 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-ser124tyr (accessed [today's date]).

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