Is THRB p.Leu11Val (c.31C>G) pathogenic?

THRB p.Leu11Val (c.31C>G) is classified Uncertain significance in THRB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-24). AlphaMissense: likely benign (0.0663); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with THRB p.Leu11Val (c.31C>G)?

THRB p.Leu11Val (c.31C>G) is associated with Inborn genetic diseases (ClinVar).

How common is THRB p.Leu11Val (c.31C>G) in the general population?

THRB p.Leu11Val (c.31C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about THRB p.Leu11Val (c.31C>G)?

AlphaMissense predicts likely benign (score 0.0663) — an in-silico prediction, not a clinical call.

THRB p.Leu11Val

c.31C>G · rs2474276508 · VCV2529654

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0663 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0663	likely benign
REVEL	0.502	indeterminate
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 76 kb · p 0.02 · regional, not allelic
Overall
CADD	25.5	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: THRB
Protein: p.Leu11Val
Coding: c.31C>G
MANE Select: NM_001354712
dbSNP: rs2474276508
Type: single nucleotide variant
Location: chr3:24190326 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.24 · 34 PDB
Residue 11: the 'modulating' region

Full THRB 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

THRB p.Glu449Ter Likely pathogenic ★★ same condition
THRB p.Glu217Lys Uncertain significance ★★ ⚠ same condition
THRB p.Arg46Cys Uncertain significance ★ ⚠ same condition
THRB p.Asp154Glu Uncertain significance ★ ⚠ same condition
THRB p.Asp73Glu Uncertain significance ★ ⚠ same condition
THRB p.Gln53His Conflicting classifications of pathogenicity ★ ⚠ same condition
THRB p.Glu404Gly Uncertain significance ★ ⚠ same condition
THRB p.Glu8Ala 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/thrb-p-leu11val (accessed [today's date]).

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