Is CTF1 p.Pro116Leu (c.347C>T) pathogenic?

CTF1 p.Pro116Leu (c.347C>T) is classified Uncertain significance in CTF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-22). AlphaMissense: likely benign (0.1194); Ultra-rare (popmax 0.0275%, eas).

How common is CTF1 p.Pro116Leu (c.347C>T) in the general population?

CTF1 p.Pro116Leu (c.347C>T) is ultra-rare (popmax 0.0275%, eas) (gnomAD).

What do computational predictors say about CTF1 p.Pro116Leu (c.347C>T)?

AlphaMissense predicts likely benign (score 0.1194) — an in-silico prediction, not a clinical call.

CTF1 p.Pro116Leu

c.347C>T · rs886051924 · VCV2732186

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1194 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0275%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1194	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -10.10	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.42	GERP -2.6
Regional constraint	o/e 0.94	unconstrained · MANE · 5,892 bp · p 0.33 · regional, not allelic
Overall
CADD	8.407	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 0.0275% East Asian · 3/10,898 alleles

Filtering AF 0.00746% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00391%

Overall 0.000388% 4/1,031,310 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0275%	3,633
African / African-American	0.00173%	57,742

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.Pro116Leu
Coding: c.347C>T
MANE Select: NM_001330
dbSNP: rs886051924
Type: single nucleotide variant
Location: chr16:30902280 (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.Pro116Arg Uncertain significance ★★ ⚠ same residue
CTF1 p.Pro116Ala Uncertain significance ★ ⚠ same residue
CTF1 p.Pro116_Ala125del Uncertain significance ★ same residue
CTF1 p.Pro116fs Uncertain significance ★ same residue
CTF1 p.Pro116Thr Uncertain significance ★ same residue
CTF1 c.*5C>A Uncertain significance ★★ same type
CTF1 p.Ala156Thr Uncertain significance ★★ ⚠ same type
CTF1 p.Ala34Val 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-pro116leu (accessed [today's date]).

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