Is TMPRSS6 p.Ser130= (c.390C>T) pathogenic?

TMPRSS6 p.Ser130= (c.390C>T) is classified Benign/Likely benign in TMPRSS6 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-04). Low-frequency (popmax 1.71%, afr); Associated with microcytic anemia.

What condition is associated with TMPRSS6 p.Ser130= (c.390C>T)?

TMPRSS6 p.Ser130= (c.390C>T) is associated with microcytic anemia (ClinVar).

How common is TMPRSS6 p.Ser130= (c.390C>T) in the general population?

TMPRSS6 p.Ser130= (c.390C>T) is low-frequency (popmax 1.71%, afr) (gnomAD).

TMPRSS6 p.Ser130=

c.390C>T · rs147700428 · VCV899547

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.71%, afr)

Conditions

microcytic anemia

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 -7.1	GERP -3
Overall
CADD	1.124	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.71% African / African-American · 1,270/74,092 alleles

Filtering AF 1.64% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.6%

Overall 0.109% 1,706/1,564,804 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.71%	58
Middle Eastern	0.167%	600
Admixed American	0.141%	710
Remaining individualsnot grpmax-eligible	0.115%	867
European (non-Finnish)	0.0237%	4,226
South Asian	0.00708%	14,127
East Asian	0.00702%	14,249

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: TMPRSS6
Protein: p.Ser130=
Coding: c.390C>T
MANE Select: NM_001374504
dbSNP: rs147700428
Type: single nucleotide variant
Location: chr22:37096662 (GRCh38)
Gene constraint: LOEUF 0.821 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.69 · 1 PDB
Residue 130: the sea domain; an α-helix

Full TMPRSS6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

microcytic anemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TMPRSS6 p.Arg590Ter Pathogenic/Likely pathogenic ★★ same condition
TMPRSS6 p.Asp512Asn Likely pathogenic ★★ same condition
TMPRSS6 p.Ala700Val Uncertain significance ★★ ⚠ same condition
TMPRSS6 p.Arg43Cys Uncertain significance ★★ ⚠ same condition
TMPRSS6 p.Arg545Trp Uncertain significance ★★ ⚠ same condition
TMPRSS6 p.Arg735His Uncertain significance ★★ ⚠ same condition
TMPRSS6 p.Arg96His Uncertain significance ★★ ⚠ same condition
TMPRSS6 p.Glu151Lys 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/tmprss6-p-ser130 (accessed [today's date]).

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