Is MAT1A p.Ser170= (c.510C>T) pathogenic?

MAT1A p.Ser170= (c.510C>T) is classified Likely benign in MAT1A (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-02). Ultra-rare (popmax 0.0245%, eas); Associated with methionine adenosyltransferase deficiency.

What condition is associated with MAT1A p.Ser170= (c.510C>T)?

MAT1A p.Ser170= (c.510C>T) is associated with methionine adenosyltransferase deficiency (ClinVar).

How common is MAT1A p.Ser170= (c.510C>T) in the general population?

MAT1A p.Ser170= (c.510C>T) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

MAT1A p.Ser170=

Q: How is Methionine adenosyltransferase I/III deficiency inherited?

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

c.510C>T · rs763409751 · VCV738907

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Conditions

methionine adenosyltransferase deficiency

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 -15	GERP -3.7
Overall
CADD	0.031	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% East Asian · 11/44,864 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00279% 45/1,613,952 alleles · ultra-rare exomes 40/1,461,862 · genomes 5/152,090 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0288%	3,471
East Asiangrpmax	0.0245%	4,079
Admixed American	0.00833%	12,000
South Asian	0.00549%	18,214
African / African-American	0.00267%	37,450
European (non-Finnish)	0.000339%	295,008

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MAT1A
Protein: p.Ser170=
Coding: c.510C>T
MANE Select: NM_000429
dbSNP: rs763409751
Type: single nucleotide variant
Location: chr10:80280212 (GRCh38)
Gene constraint: LOEUF 0.653 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 96.77 · 4 PDB
Residue 170: an α-helix

Full MAT1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

methionine adenosyltransferase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Methionine adenosyltransferase I/III deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

MAT1A p.Ser170Pro Uncertain significance ★★ ⚠ same residue
MAT1A p.Ala259Val Pathogenic ★★ same condition
MAT1A p.Arg199Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
MAT1A p.Arg199His Pathogenic ★★ ⚠ same condition
MAT1A p.Arg264Cys Pathogenic ★★ same condition
MAT1A p.Arg264His Pathogenic ★★ same condition
MAT1A p.Arg292Cys Pathogenic/Likely pathogenic ★★ same condition
MAT1A p.Arg299Cys Pathogenic/Likely 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/mat1a-p-ser170 (accessed [today's date]).

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