Is CTF1 p.Ala41Ser (c.121G>T) pathogenic?

CTF1 p.Ala41Ser (c.121G>T) is classified Conflicting classifications of pathogenicity in CTF1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-16). AlphaMissense: likely benign (0.1485); Ultra-rare (popmax 0.0165%, mid).

How common is CTF1 p.Ala41Ser (c.121G>T) in the general population?

CTF1 p.Ala41Ser (c.121G>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CTF1 p.Ala41Ser (c.121G>T)?

AlphaMissense predicts likely benign (score 0.1485) — an in-silico prediction, not a clinical call.

CTF1 p.Ala41Ser

c.121G>T · rs149342494 · VCV1652038

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1485 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1485	likely benign
REVEL	0.503	indeterminate
SaProt	LLR -7.94	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 5,892 bp · p 0.33 · regional, not allelic
Overall
CADD	21.9	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 0.0165% Middle Eastern · 1/6,070 alleles

Filtering AF 0.0043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.00454% 73/1,608,996 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.132%	756
Middle Easterngrpmax	0.0165%	6,070
Remaining individualsnot grpmax-eligible	0.0144%	6,923
Admixed American	0.0101%	9,947
African / African-American	0.00268%	37,254
European (non-Finnish)	0.00127%	78,443
South Asian	0.0011%	90,874

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala41Ser
Coding: c.121G>T
MANE Select: NM_001330
dbSNP: rs149342494
Type: single nucleotide variant
Location: chr16:30899510 (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 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
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-ala41ser (accessed [today's date]).

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