Is TIMCC p.Ala60= (c.180C>T) pathogenic?

TIMCC p.Ala60= (c.180C>T) is classified Likely benign in TIMCC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). Ultra-rare (popmax 0.0119%, sas).

How common is TIMCC p.Ala60= (c.180C>T) in the general population?

TIMCC p.Ala60= (c.180C>T) is ultra-rare (popmax 0.0119%, sas) (gnomAD).

TIMCC p.Ala60=

c.180C>T · VCV4955470

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0119%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.79	GERP 1.1
Overall
CADD	4.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0119% South Asian · 10/83,870 alleles

Filtering AF 0.00641% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00488%

Overall 0.00129% 20/1,549,856 alleles · ultra-rare exomes 19/1,397,480 · genomes 1/152,376 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0119%	8,387
Remaining individualsnot grpmax-eligible	0.005%	20,009
European (non-Finnish)	0.000611%	163,749

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: TIMCC
Protein: p.Ala60=
Coding: c.180C>T
MANE Select: NM_001329752
Type: single nucleotide variant
Location: chr2:70301832 (GRCh38)
Structure: AlphaFold pLDDT 95.42

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

Similar variants

TIMCC p.Asn24= Benign/Likely benign ★★ same type
FAM136A p.Gln183Ter Pathogenic ★ same type
FAM136A p.Ala12Val Uncertain significance ★ ⚠ same type
FAM136A p.Ala144Thr Uncertain significance ★ same type
FAM136A p.Ala203Asp Uncertain significance ★ ⚠ same type
FAM136A p.Ala2Val Uncertain significance ★ ⚠ same type
FAM136A p.Arg163Gly Uncertain significance ★ ⚠ same type
FAM136A p.Gln10His 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/timcc-p-ala60 (accessed [today's date]).

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