Is CTF1 p.Ala92Glu (c.275C>A) pathogenic?

CTF1 p.Ala92Glu (c.275C>A) is classified Conflicting classifications of pathogenicity in CTF1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1401); Rare (popmax 0.245%, amr); Associated with Dilated Cardiomyopathy, Dominant.

What condition is associated with CTF1 p.Ala92Glu (c.275C>A)?

CTF1 p.Ala92Glu (c.275C>A) is associated with Dilated Cardiomyopathy, Dominant, hypertrophic cardiomyopathy (ClinVar).

How common is CTF1 p.Ala92Glu (c.275C>A) in the general population?

CTF1 p.Ala92Glu (c.275C>A) is rare (popmax 0.245%, amr) (gnomAD).

What do computational predictors say about CTF1 p.Ala92Glu (c.275C>A)?

AlphaMissense predicts likely benign (score 0.1401) — an in-silico prediction, not a clinical call.

CTF1 p.Ala92Glu

c.275C>A · rs727502949 · VCV163017

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1401 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.245%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Dilated Cardiomyopathy, Dominant

Computational evidence

Protein change
AlphaMissense	0.1401	likely benign
REVEL	0.286	benign-leaning
SaProt	LLR -6.59	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 1.1	GERP -2.4, phastCons 0.25
Regional constraint	o/e 0.94	unconstrained · MANE · 5,892 bp · p 0.33 · regional, not allelic
Overall
CADD	15.57	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 0.245% Admixed American · 52/21,252 alleles

Filtering AF 0.192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.173%

Overall 0.00445% 52/1,167,266 alleles · rare

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.Ala92Glu
Coding: c.275C>A
MANE Select: NM_001330
dbSNP: rs727502949
Type: single nucleotide variant
Location: chr16:30902208 (GRCh38)
Gene constraint: LOEUF 1.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.94
Residue 92: a UniProt-annotated variant site (in)

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

Disease context

Dilated Cardiomyopathy, Dominant

Also linked: hypertrophic cardiomyopathy

Similar variants

CTF1 p.Ala92Thr Conflicting classifications of pathogenicity ★ same residue
CTF1 p.Pro98Leu Uncertain significance ★★ ⚠ same condition
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

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-ala92glu (accessed [today's date]).

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