Is TG p.Ser913Pro (c.2737T>C) pathogenic?

TG p.Ser913Pro (c.2737T>C) is classified Uncertain significance in TG (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.1695); Very rare (popmax 0.00517%, nfe); Associated with thyroid dyshormonogenesis 3.

What condition is associated with TG p.Ser913Pro (c.2737T>C)?

TG p.Ser913Pro (c.2737T>C) is associated with thyroid dyshormonogenesis 3 (ClinVar).

How common is TG p.Ser913Pro (c.2737T>C) in the general population?

TG p.Ser913Pro (c.2737T>C) is very rare (popmax 0.00517%, nfe) (gnomAD).

How is Familial thyroid dyshormonogenesis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about TG p.Ser913Pro (c.2737T>C)?

AlphaMissense predicts likely benign (score 0.1695) — an in-silico prediction, not a clinical call.

TG p.Ser913Pro

c.2737T>C · rs773538206 · VCV361929

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1695 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

thyroid dyshormonogenesis 3

Computational evidence

Protein change
AlphaMissense	0.1695	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP -4.2, phastCons 0.003
Regional constraint	o/e 1.04	unconstrained · MANE · 268 kb · p 0.022 · regional, not allelic
Overall
CADD	9.033	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00517% European (non-Finnish) · 61/1,179,488 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00397% 64/1,611,686 alleles · very rare exomes 63/1,459,626 · genomes 1/152,060 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,336
Remaining individualsnot grpmax-eligible	0.00481%	20,779

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TG
Protein: p.Ser913Pro
Coding: c.2737T>C
MANE Select: NM_003235
dbSNP: rs773538206
Type: single nucleotide variant
Location: chr8:132888544 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Residue 913: an α-helix; the thyroglobulin type-1 7 domain

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

Disease context

thyroid dyshormonogenesis 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial thyroid dyshormonogenesis (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

TG c.274+2T>G Pathogenic ★★ same condition
TG c.3634+1G>A Likely pathogenic ★★ same condition
TG c.5686+1G>A Pathogenic ★★ same condition
TG c.5686+1G>T Pathogenic ★★ same condition
TG c.638+5G>A Pathogenic/Likely pathogenic ★★ same condition
TG c.6782+1G>T Likely pathogenic ★★ same condition
TG c.7863-1G>A Likely pathogenic ★★ same condition
TG p.Arg1530Ter 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/tg-p-ser913pro (accessed [today's date]).

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