Is TMC8 p.Gln337Arg (c.1010A>G) pathogenic?

TMC8 p.Gln337Arg (c.1010A>G) is classified Uncertain significance in TMC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-17). AlphaMissense: likely benign (0.2481); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TMC8 p.Gln337Arg (c.1010A>G)?

TMC8 p.Gln337Arg (c.1010A>G) is associated with Inborn genetic diseases (ClinVar).

How common is TMC8 p.Gln337Arg (c.1010A>G) in the general population?

TMC8 p.Gln337Arg (c.1010A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TMC8 p.Gln337Arg (c.1010A>G)?

AlphaMissense predicts likely benign (score 0.2481) — an in-silico prediction, not a clinical call.

TMC8 p.Gln337Arg

c.1010A>G · rs2510792339 · VCV2526194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2481 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2481	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -7.50	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 11	GERP 0.46, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 9,520 bp · p 0.44 · regional, not allelic
Overall
CADD	26.2	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

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: TMC8
Protein: p.Gln337Arg
Coding: c.1010A>G
MANE Select: NM_152468
dbSNP: rs2510792339
Type: single nucleotide variant
Location: chr17:78134892 (GRCh38)
Gene constraint: LOEUF 1.201 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.77

Full TMC8 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

TMC8 p.Ala313Val Uncertain significance ★★ ⚠ same condition
TMC8 p.Arg202Cys Uncertain significance ★★ ⚠ same condition
TMC8 p.Arg279His Uncertain significance ★★ ⚠ same condition
TMC8 p.Arg466Trp Uncertain significance ★★ ⚠ same condition
TMC8 p.Arg629Leu Uncertain significance ★★ same condition
TMC8 p.Arg719His Uncertain significance ★★ ⚠ same condition
TMC8 p.Asn412Ser Uncertain significance ★★ ⚠ same condition
TMC8 p.His626Tyr 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/tmc8-p-gln337arg (accessed [today's date]).

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