Is TIMCC p.Ala54Val (c.161C>T) pathogenic?

TIMCC p.Ala54Val (c.161C>T) is classified Likely benign in TIMCC (ClinVar, Single submitter, 2 submitters; last evaluated 2023-12-13). Rare (popmax 0.797%, afr).

How common is TIMCC p.Ala54Val (c.161C>T) in the general population?

TIMCC p.Ala54Val (c.161C>T) is rare (popmax 0.797%, afr) (gnomAD).

TIMCC p.Ala54Val

c.161C>T · rs111492861 · VCV3049056

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.797%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.016	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.29	GERP 0.006
Regional constraint	o/e 1.02	unconstrained · MANE · 4,719 bp · p 0.74 · regional, not allelic
Overall
CADD	15.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.797% African / African-American · 584/73,294 alleles

Filtering AF 0.743% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.722%

Overall 0.0409% 635/1,552,748 alleles · rare exomes 275/1,400,364 · genomes 360/152,384 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.797%	126
Middle Eastern	0.0512%	1,953
Remaining individualsnot grpmax-eligible	0.0465%	2,149
Admixed American	0.0313%	3,193
European (non-Finnish)	0.000348%	286,972

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.Ala54Val
Coding: c.161C>T
MANE Select: NM_001329752
dbSNP: rs111492861
Type: single nucleotide variant
Location: chr2:70301851 (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-ala54val (accessed [today's date]).

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