Is THRB p.Ser314Cys (c.941C>G) pathogenic?

THRB p.Ser314Cys (c.941C>G) is classified Likely pathogenic in THRB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-20). AlphaMissense: likely pathogenic (0.6307); Absent from gnomAD v4.1; Associated with THRB-related disorder.

What condition is associated with THRB p.Ser314Cys (c.941C>G)?

THRB p.Ser314Cys (c.941C>G) is associated with THRB-related disorder (ClinVar).

How common is THRB p.Ser314Cys (c.941C>G) in the general population?

THRB p.Ser314Cys (c.941C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about THRB p.Ser314Cys (c.941C>G)?

AlphaMissense predicts likely pathogenic (score 0.6307) — an in-silico prediction, not a clinical call.

THRB p.Ser314Cys

c.941C>G · VCV4961506

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6307 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

THRB-related disorder

Computational evidence

Protein change
AlphaMissense	0.6307	likely pathogenic ✓ concordant with ClinVar
REVEL	0.757	pathogenic-leaning
SaProt	LLR -5.75	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.29	constrained · MANE · 10 kb · p 5.8e-19 · regional, not allelic
Overall
CADD	32.0	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

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.Ser314Cys
Coding: c.941C>G
MANE Select: NM_001354712
Type: single nucleotide variant
Location: chr3:24127702 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.24 · 34 PDB
Residue 314: the nr lbd domain; the 'interaction with nr2f6' region; an α-helix

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

Disease context

THRB-related disorder

Similar variants

THRB p.Ser314Phe Pathogenic ⚠ same residue
THRB p.Arg316His Pathogenic ★★ same condition
THRB p.Arg383His Pathogenic/Likely pathogenic ★★ same condition
THRB p.Arg438Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
THRB p.Gly332Glu Likely pathogenic ★★ same condition
THRB p.His435Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
THRB p.Ile250Thr Likely pathogenic ★★ ⚠ same condition
THRB p.Ile431Thr 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/thrb-p-ser314cys (accessed [today's date]).

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