Is TMC1 p.Leu157= (c.471C>T) pathogenic?

TMC1 p.Leu157= (c.471C>T) is classified Likely benign in TMC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-17). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TMC1 p.Leu157= (c.471C>T)?

TMC1 p.Leu157= (c.471C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TMC1 p.Leu157= (c.471C>T) in the general population?

TMC1 p.Leu157= (c.471C>T) is absent from gnomAD v4.1 (gnomAD).

TMC1 p.Leu157=

c.471C>T · VCV4839971

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

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 -1.2	GERP -3, phastCons 0.001
Overall
CADD	4.839	PHRED · no single calibrated threshold — expert panels disagree

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: TMC1
Protein: p.Leu157=
Coding: c.471C>T
MANE Select: NM_138691
Type: single nucleotide variant
Location: chr9:72742461 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 1 PDB

Full TMC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TMC1 p.Trp588Ter Pathogenic ★★ same condition
TMC1 p.Ala150Thr Uncertain significance ★★ ⚠ same condition
TMC1 p.Ala394Ser Uncertain significance ★★ ⚠ same condition
TMC1 p.Ala690Thr Uncertain significance ★★ ⚠ same condition
TMC1 p.Arg141Gln Uncertain significance ★★ ⚠ same condition
TMC1 p.Arg264Gln Uncertain significance ★★ same condition
TMC1 p.Arg264Pro Uncertain significance ★★ ⚠ same condition
TMC1 p.Arg512Gln 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/tmc1-p-leu157 (accessed [today's date]).

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