Is TXNRD2 p.Ser387= (c.1161A>G) pathogenic?

TXNRD2 p.Ser387= (c.1161A>G) is classified Likely benign in TXNRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-14). Ultra-rare (popmax 0.0165%, mid); Associated with Cardiovascular phenotype.

What condition is associated with TXNRD2 p.Ser387= (c.1161A>G)?

TXNRD2 p.Ser387= (c.1161A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is TXNRD2 p.Ser387= (c.1161A>G) in the general population?

TXNRD2 p.Ser387= (c.1161A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

TXNRD2 p.Ser387=

c.1161A>G · rs777907161 · VCV1736767

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 -1.6	GERP -1.5
Overall
CADD	1.415	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,362 alleles · ultra-rare exomes 5/1,461,048 · genomes 0/152,314 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	0.000339%	295,004

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.Ser387=
Coding: c.1161A>G
MANE Select: NM_006440
dbSNP: rs777907161
Type: single nucleotide variant
Location: chr22:19880643 (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

Similar variants

TXNRD2 p.Ser387Pro Uncertain significance ★ same residue
TXNRD2 c.104-3C>G Uncertain significance ★★ same condition
TXNRD2 c.1182+5G>A Uncertain significance ★★ same condition
TXNRD2 c.172+3A>G Uncertain significance ★★ same condition
TXNRD2 c.450-1G>A Uncertain significance ★★ same condition
TXNRD2 c.528+2T>C Uncertain significance ★★ same condition
TXNRD2 c.591+1G>A Uncertain significance ★★ same condition
TXNRD2 c.662+1G>A 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-ser387 (accessed [today's date]).

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