Is TOM1 p.Asp393= (c.1179C>T) pathogenic?

TOM1 p.Asp393= (c.1179C>T) is classified Likely benign in TOM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). Rare (popmax 0.151%, sas).

How common is TOM1 p.Asp393= (c.1179C>T) in the general population?

TOM1 p.Asp393= (c.1179C>T) is rare (popmax 0.151%, sas) (gnomAD).

TOM1 p.Asp393=

c.1179C>T · rs199955093 · VCV2653090

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.151%, sas)

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 -11	GERP -3.7
Overall
CADD	8.748	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.151% South Asian · 134/88,542 alleles

Filtering AF 0.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.0251% 402/1,599,454 alleles · rare exomes 362/1,447,298 · genomes 40/152,156 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.5%	200
South Asiangrpmax	0.151%	661
Middle Eastern	0.0331%	3,018
Remaining individualsnot grpmax-eligible	0.0275%	3,642
African / African-American	0.012%	8,301
European (non-Finnish)	0.00741%	13,492
Admixed American	0.00693%	14,436
East Asian	0.00679%	14,728

Ashkenazi Jewish 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: TOM1
Protein: p.Asp393=
Coding: c.1179C>T
MANE Select: NM_005488
dbSNP: rs199955093
Type: single nucleotide variant
Location: chr22:35338743 (GRCh38)
Gene constraint: LOEUF 0.866 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 6 PDB
Residue 393: the 'interaction with myo6' region

Full TOM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TOM1 p.Ala401Pro Uncertain significance ★★ ⚠ same type
TOM1 p.Arg450Gln Uncertain significance ★★ ⚠ same type
TOM1 p.Asp324Asn Uncertain significance ★★ ⚠ same type
TOM1 p.Ile40Val Uncertain significance ★★ ⚠ same type
TOM1 p.Ser461Phe Uncertain significance ★★ ⚠ same type
TOM1 p.Asp38= Benign ★★ same type
TOM1 p.Ser235= Benign ★★ same type
TOM1 c.1028-8C>T 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/tom1-p-asp393 (accessed [today's date]).

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