Is CTF1 p.Ala34Val (c.101C>T) pathogenic?

CTF1 p.Ala34Val (c.101C>T) is classified Uncertain significance in CTF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-11). AlphaMissense: ambiguous (0.4015); Ultra-rare (popmax 0.0156%, eas).

How common is CTF1 p.Ala34Val (c.101C>T) in the general population?

CTF1 p.Ala34Val (c.101C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about CTF1 p.Ala34Val (c.101C>T)?

AlphaMissense predicts ambiguous (score 0.4015) — an in-silico prediction, not a clinical call.

CTF1 p.Ala34Val

c.101C>T · rs753956418 · VCV2144950

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4015 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Computational evidence

Protein change
AlphaMissense	0.4015	ambiguous
REVEL	0.478	indeterminate
SaProt	LLR -10.01	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 5,892 bp · p 0.33 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,838 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00136% 22/1,613,206 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,405
Admixed American	0.00167%	59,922
Remaining individualsnot grpmax-eligible	0.0016%	62,454
African / African-American	0.00134%	74,706
South Asian	0.0011%	91,054
European (non-Finnish)	0.000932%	107,246

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: CTF1
Protein: p.Ala34Val
Coding: c.101C>T
MANE Select: NM_001330
dbSNP: rs753956418
Type: single nucleotide variant
Location: chr16:30899490 (GRCh38)
Gene constraint: LOEUF 1.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.94

Full CTF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTF1 p.Ala34= Likely benign ★ same residue
CTF1 c.*5C>A Uncertain significance ★★ same type
CTF1 p.Ala156Thr Uncertain significance ★★ ⚠ same type
CTF1 p.Arg107Ser Uncertain significance ★★ ⚠ same type
CTF1 p.Arg176His Uncertain significance ★★ ⚠ same type
CTF1 p.Arg65Gln Uncertain significance ★★ ⚠ same type
CTF1 p.Asp191Glu Uncertain significance ★★ ⚠ same type
CTF1 p.Asp54Glu 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/ctf1-p-ala34val (accessed [today's date]).

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