Is LIPA p.Val206Phe (c.616G>T) pathogenic?

LIPA p.Val206Phe (c.616G>T) is classified Uncertain significance in LIPA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-09). AlphaMissense: ambiguous (0.464); Very rare (popmax 0.00134%, afr); Associated with Cardiovascular phenotype.

What condition is associated with LIPA p.Val206Phe (c.616G>T)?

LIPA p.Val206Phe (c.616G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is LIPA p.Val206Phe (c.616G>T) in the general population?

LIPA p.Val206Phe (c.616G>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about LIPA p.Val206Phe (c.616G>T)?

AlphaMissense predicts ambiguous (score 0.464) — an in-silico prediction, not a clinical call.

LIPA p.Val206Phe

c.616G>T · VCV4859210

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.464 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.464	ambiguous
REVEL	0.281	benign-leaning
SaProt	LLR -11.58	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.9
Overall
CADD	0.005	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 0.00134% African / African-American · 1/74,896 alleles

Overall 0.000657% 1/152,124 alleles · very rare

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: LIPA
Protein: p.Val206Phe
Coding: c.616G>T
MANE Select: NM_006552 · reported on NM_000235
Type: single nucleotide variant
Location: chr10:89225151 (GRCh38)
Structure: AlphaFold pLDDT 89.74

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LIPA p.Val206= Likely benign ★★ same residue
LIPA p.Val206Leu Likely benign ★ same residue
LIPA p.Val206Ile Uncertain significance ★★ ⚠ same residue
LIPA p.Ala307Asp Likely pathogenic ★★ same condition
LIPA p.Leu200Pro Pathogenic ★★ same condition
LIPA p.Val206dup Likely pathogenic ★★ same residue
LIPA p.Asp349Gly Uncertain significance ★★ same condition
LIPA p.Gln186His 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/lipa-p-val206phe (accessed [today's date]).

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