Is TMPRSS6 p.Asp600Val (c.1799A>T) pathogenic?

TMPRSS6 p.Asp600Val (c.1799A>T) is classified Uncertain significance in TMPRSS6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-23). AlphaMissense: likely pathogenic (0.5783); Very rare (popmax 0.00254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TMPRSS6 p.Asp600Val (c.1799A>T)?

TMPRSS6 p.Asp600Val (c.1799A>T) is associated with Inborn genetic diseases (ClinVar).

How common is TMPRSS6 p.Asp600Val (c.1799A>T) in the general population?

TMPRSS6 p.Asp600Val (c.1799A>T) is very rare (popmax 0.00254%, nfe) (gnomAD).

What do computational predictors say about TMPRSS6 p.Asp600Val (c.1799A>T)?

AlphaMissense predicts likely pathogenic (score 0.5783) — an in-silico prediction, not a clinical call.

TMPRSS6 p.Asp600Val

c.1799A>T · VCV3327355

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5783 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00254%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5783	likely pathogenic
REVEL	0.796	moderately pathogenic-leaning
SaProt	LLR -11.30	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.91, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 37 kb · p 0.097 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D609V vs ClinVar D600V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00254% European (non-Finnish) · 30/1,180,004 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00198% 32/1,613,200 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00254%	39,334
Remaining individualsnot grpmax-eligible	0.0016%	62,476
African / African-American	0.00134%	74,882

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.Asp600Val
Coding: c.1799A>T
MANE Select: NM_001374504
Type: single nucleotide variant
Location: chr22:37070526 (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 600: the peptidase s1 domain; a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TMPRSS6 p.Asp600= Benign/Likely benign ★★ same residue
TMPRSS6 p.Ala164Thr Uncertain significance ★★ ⚠ same condition
TMPRSS6 p.Ala700Val Uncertain significance ★★ ⚠ same condition
TMPRSS6 p.Arg121His Uncertain significance ★★ ⚠ same condition
TMPRSS6 p.Arg251Gln Uncertain significance ★★ ⚠ same condition
TMPRSS6 p.Arg545Trp Uncertain significance ★★ ⚠ same condition
TMPRSS6 p.Arg780Gln Uncertain significance ★★ ⚠ same condition
TMPRSS6 p.Arg96His 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-asp600val (accessed [today's date]).

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