Is TXNRD2 p.Ala101= (c.303A>G) pathogenic?

TXNRD2 p.Ala101= (c.303A>G) is classified Likely benign in TXNRD2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-11). Rare (popmax 0.111%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with TXNRD2 p.Ala101= (c.303A>G)?

TXNRD2 p.Ala101= (c.303A>G) is associated with Cardiovascular phenotype, dilated cardiomyopathy (ClinVar).

How common is TXNRD2 p.Ala101= (c.303A>G) in the general population?

TXNRD2 p.Ala101= (c.303A>G) is rare (popmax 0.111%, nfe) (gnomAD).

TXNRD2 p.Ala101=

c.303A>G · rs200076623 · VCV264127

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.111%, nfe)

Conditions

Cardiovascular phenotype

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 -11	GERP -3.8
Overall
CADD	0.961	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.111% European (non-Finnish) · 1,310/1,179,946 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.0872% 1,406/1,612,990 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.111%	901
Admixed American	0.07%	1,428
Remaining individualsnot grpmax-eligible	0.0576%	1,736
Middle Eastern	0.0165%	6,058
African / African-American	0.0147%	6,818
Finnishnot grpmax-eligible	0.00633%	15,795
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
South Asian	0.0011%	91,068

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: TXNRD2
Protein: p.Ala101=
Coding: c.303A>G
MANE Select: NM_006440
dbSNP: rs200076623
Type: single nucleotide variant
Location: chr22:19918931 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)

Full TXNRD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy

Similar variants

TXNRD2 p.Ala101Thr Uncertain significance ★ same residue
TXNRD2 p.Ala101Val Uncertain significance ★ same residue
TXNRD2 c.104-1G>A Uncertain significance ★★ same condition
TXNRD2 c.104-3C>G Uncertain significance ★★ same condition
TXNRD2 c.1086+4C>T Uncertain significance ★★ same condition
TXNRD2 c.1087-2A>G Uncertain significance ★★ same condition
TXNRD2 c.1182+5G>A Uncertain significance ★★ same condition
TXNRD2 c.1348-2A>G 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/txnrd2-p-ala101 (accessed [today's date]).

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