Is CTF1 p.Ala152Pro (c.454G>C) pathogenic?

CTF1 p.Ala152Pro (c.454G>C) is classified Conflicting classifications of pathogenicity in CTF1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-03). AlphaMissense: likely benign (0.0538); Very rare (popmax 0.00316%, afr).

How common is CTF1 p.Ala152Pro (c.454G>C) in the general population?

CTF1 p.Ala152Pro (c.454G>C) is very rare (popmax 0.00316%, afr) (gnomAD).

What do computational predictors say about CTF1 p.Ala152Pro (c.454G>C)?

AlphaMissense predicts likely benign (score 0.0538) — an in-silico prediction, not a clinical call.

CTF1 p.Ala152Pro

c.454G>C · rs1467275471 · VCV478119

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0538 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00316%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0538	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -5.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -1.4
Regional constraint	o/e 0.94	unconstrained · MANE · 5,892 bp · p 0.33 · regional, not allelic
Overall
CADD	0.733	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 0.00316% African / African-American · 2/63,200 alleles

Filtering AF 0.000525% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000309%

Overall 0.00105% 13/1,239,092 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00316%	31,600
South Asian	0.00291%	34,312
Remaining individualsnot grpmax-eligible	0.00224%	44,640
European (non-Finnish)	0.000908%	110,125

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.Ala152Pro
Coding: c.454G>C
MANE Select: NM_001330
dbSNP: rs1467275471
Type: single nucleotide variant
Location: chr16:30902387 (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.Ala152= Likely benign ★ same residue
CTF1 c.*5C>A Uncertain significance ★★ same type
CTF1 p.Ala156Thr Uncertain significance ★★ ⚠ same type
CTF1 p.Ala34Val 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

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-ala152pro (accessed [today's date]).

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