Is APOLTP p.Ser2169= (c.6507C>T) pathogenic?

APOLTP p.Ser2169= (c.6507C>T) is classified Likely benign in APOLTP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Ultra-rare (popmax 0.0721%, nfe).

How common is APOLTP p.Ser2169= (c.6507C>T) in the general population?

APOLTP p.Ser2169= (c.6507C>T) is ultra-rare (popmax 0.0721%, nfe) (gnomAD).

APOLTP p.Ser2169=

c.6507C>T · rs757047691 · VCV2646220

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0721%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.8	GERP -1.6
Overall
CADD	0.212	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0721% European (non-Finnish) · 163/226,170 alleles

Filtering AF 0.0629% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0595%

Overall 0.0473% 189/399,190 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0721%	1,388
Middle Eastern	0.0629%	1,590
Remaining individualsnot grpmax-eligible	0.0595%	1,680
Finnishnot grpmax-eligible	0.0188%	5,312
Admixed American	0.0176%	5,686
South Asian	0.0127%	7,856
African / African-American	0.00615%	16,257

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: APOLTP
Protein: p.Ser2169=
Coding: c.6507C>T
MANE Select: NM_001370704
dbSNP: rs757047691
Type: single nucleotide variant
Location: chr16:11417717 (GRCh38)
Structure: AlphaFold pLDDT 87.88

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

Similar variants

APOLTP p.Arg1455Gln Likely benign ★ same type
APOLTP p.Arg179= Likely benign ★ same type
APOLTP p.Asn1704= Likely benign ★ same type
APOLTP p.Glu2187= Likely benign ★ same type
APOLTP p.His1059= Likely benign ★ same type
APOLTP p.His897= Likely benign ★ same type
APOLTP p.Lys2349= Likely benign ★ same type
APOLTP p.Pro1959= Likely benign ★ 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/apoltp-p-ser2169 (accessed [today's date]).

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