Is BLTP3A p.Ala720Val (c.2159C>T) pathogenic?

BLTP3A p.Ala720Val (c.2159C>T) is classified Uncertain significance in BLTP3A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-09). AlphaMissense: likely benign (0.1212); Ultra-rare (popmax 0.0174%, afr).

How common is BLTP3A p.Ala720Val (c.2159C>T) in the general population?

BLTP3A p.Ala720Val (c.2159C>T) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

What do computational predictors say about BLTP3A p.Ala720Val (c.2159C>T)?

AlphaMissense predicts likely benign (score 0.1212) — an in-silico prediction, not a clinical call.

BLTP3A p.Ala720Val

c.2159C>T · rs200349469 · VCV2482540

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1212 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1212	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -8.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 80 kb · p 4.8e-07 · regional, not allelic
Overall
CADD	23.7	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 0.0174% African / African-American · 13/74,902 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.000929% 15/1,614,032 alleles · ultra-rare exomes 3/1,461,890 · genomes 12/152,142 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,762
Admixed American	0.00167%	59,988
European (non-Finnish)	8.47e-05%	1,180,058

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: BLTP3A
Protein: p.Ala720Val
Coding: c.2159C>T
MANE Select: NM_017754
dbSNP: rs200349469
Type: single nucleotide variant
Location: chr6:34858515 (GRCh38)
Structure: AlphaFold pLDDT 67.37

Full BLTP3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BLTP3A p.Val1190Phe Uncertain significance ★★ ⚠ same type
BLTP3A p.Ala1021Gly Uncertain significance ★ ⚠ same type
BLTP3A p.Ala1174Pro Uncertain significance ★ ⚠ same type
BLTP3A p.Ala1217Val Uncertain significance ★ ⚠ same type
BLTP3A p.Ala1366Ser Uncertain significance ★ ⚠ same type
BLTP3A p.Ala257Thr Uncertain significance ★ ⚠ same type
BLTP3A p.Ala263Ser Uncertain significance ★ ⚠ same type
BLTP3A p.Ala373Ser 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/bltp3a-p-ala720val (accessed [today's date]).

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