Is CTIF p.Arg269His (c.806G>A) pathogenic?

CTIF p.Arg269His (c.806G>A) is classified Uncertain significance in CTIF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-26). AlphaMissense: likely benign (0.116); Ultra-rare (popmax 0.0132%, sas).

How common is CTIF p.Arg269His (c.806G>A) in the general population?

CTIF p.Arg269His (c.806G>A) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

What do computational predictors say about CTIF p.Arg269His (c.806G>A)?

AlphaMissense predicts likely benign (score 0.116) — an in-silico prediction, not a clinical call.

CTIF p.Arg269His

c.806G>A · VCV3270068

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.116 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.116	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -6.47	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 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 142 kb · p 0.7 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0132% South Asian · 12/91,064 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.00273% 44/1,613,888 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,589
African / African-American	0.00668%	14,977
East Asian	0.00223%	44,872
European (non-Finnish)	0.0022%	45,385

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: CTIF
Protein: p.Arg269His
Coding: c.806G>A
MANE Select: NM_014772
Type: single nucleotide variant
Location: chr18:48758140 (GRCh38)
Gene constraint: LOEUF 0.487 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 63.13
Residue 269: the 'interaction with ncbp1/cbp80' region; the 'disordered' region

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

Similar variants

CTIF p.Arg269Cys Uncertain significance ★ ⚠ same residue
CTIF c.326+4A>G Benign ★★ same type
CTIF p.Ala63= Benign ★★ same type
CTIF p.Ile277= Benign ★★ same type
CTIF c.1071+5C>T Uncertain significance ★ same type
CTIF p.Ala181Thr Uncertain significance ★ ⚠ same type
CTIF p.Ala271Val Uncertain significance ★ ⚠ same type
CTIF p.Ala304Thr 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/ctif-p-arg269his (accessed [today's date]).

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