Is TRPV6 p.Leu320Phe (c.958C>T) pathogenic?

TRPV6 p.Leu320Phe (c.958C>T) is classified Uncertain significance in TRPV6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-18). AlphaMissense: likely pathogenic (0.6865); Absent from gnomAD v4.1; Associated with hyperparathyroidism, transient neonatal.

What condition is associated with TRPV6 p.Leu320Phe (c.958C>T)?

TRPV6 p.Leu320Phe (c.958C>T) is associated with hyperparathyroidism, transient neonatal (ClinVar).

How common is TRPV6 p.Leu320Phe (c.958C>T) in the general population?

TRPV6 p.Leu320Phe (c.958C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRPV6 p.Leu320Phe (c.958C>T)?

AlphaMissense predicts likely pathogenic (score 0.6865) — an in-silico prediction, not a clinical call.

TRPV6 p.Leu320Phe

c.958C>T · VCV4080608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6865 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hyperparathyroidism, transient neonatal

Computational evidence

Protein change
AlphaMissense	0.6865	likely pathogenic
REVEL	0.647	pathogenic-leaning
SaProt	LLR -12.41	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.24	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.3	GERP 0.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.0025 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRPV6
Protein: p.Leu320Phe
Coding: c.958C>T
MANE Select: NM_018646
Type: single nucleotide variant
Location: chr7:142875829 (GRCh38)
Gene constraint: LOEUF 0.638 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.76 · 25 PDB

Full TRPV6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hyperparathyroidism, transient neonatal — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRPV6 p.Gly451Glu Pathogenic/Likely pathogenic ★★ same condition
TRPV6 p.Gly657Arg Uncertain significance ★★ ⚠ same condition
TRPV6 p.His205Arg Uncertain significance ★★ ⚠ same condition
TRPV6 p.Thr238Arg Uncertain significance ★★ ⚠ same condition
TRPV6 p.Tyr364= Benign/Likely benign ★★ same condition
TRPV6 p.Arg425Gln Likely pathogenic ★ ⚠ same condition
TRPV6 p.Arg483Trp Likely pathogenic ★ ⚠ same condition
TRPV6 p.Cys212Tyr Likely pathogenic ★ 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/trpv6-p-leu320phe (accessed [today's date]).

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