Is INMT p.Ser121= (c.363C>T) pathogenic?

INMT p.Ser121= (c.363C>T) is classified Likely benign in INMT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-27). Ultra-rare (popmax 0.0656%, afr).

How common is INMT p.Ser121= (c.363C>T) in the general population?

INMT p.Ser121= (c.363C>T) is ultra-rare (popmax 0.0656%, afr) (gnomAD).

INMT p.Ser121=

c.363C>T · VCV3860547

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0656%, afr)

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 -8	GERP -3.2
Overall
CADD	0.156	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0656% African / African-American · 49/74,672 alleles

Filtering AF 0.0509% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0457%

Overall 0.00706% 112/1,585,710 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0656%	1,524
South Asian	0.0259%	3,860
East Asian	0.0248%	4,027
Admixed American	0.0154%	6,474
Remaining individualsnot grpmax-eligible	0.00808%	12,373
Finnishnot grpmax-eligible	0.00411%	24,321
European (non-Finnish)	0.00111%	90,249

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: INMT
Protein: p.Ser121=
Coding: c.363C>T
MANE Select: NM_006774
Type: single nucleotide variant
Location: chr7:30755422 (GRCh38)
Gene constraint: LOEUF 1.467 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.14 · 1 PDB
Residue 121: an α-helix

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

Similar variants

INMT p.Ser121Arg Uncertain significance ★ ⚠ same residue
INMT c.363-7T>A Likely benign ★★ same type
INMT p.Ala104Thr Uncertain significance ★ ⚠ same type
INMT p.Ala134Glu Uncertain significance ★ ⚠ same type
INMT p.Ala215Thr Uncertain significance ★ ⚠ same type
INMT p.Ala247Ser Uncertain significance ★ ⚠ same type
INMT p.Ala247Val Uncertain significance ★ ⚠ same type
INMT p.Arg137Trp Uncertain significance ★ ⚠ same type

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/inmt-p-ser121 (accessed [today's date]).

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