Is CTIF p.Arg26His (c.77G>A) pathogenic?

CTIF p.Arg26His (c.77G>A) is classified Uncertain significance in CTIF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-04). AlphaMissense: ambiguous (0.5501); Ultra-rare (popmax 0.0165%, mid).

How common is CTIF p.Arg26His (c.77G>A) in the general population?

CTIF p.Arg26His (c.77G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CTIF p.Arg26His (c.77G>A)?

AlphaMissense predicts ambiguous (score 0.5501) — an in-silico prediction, not a clinical call.

CTIF p.Arg26His

c.77G>A · VCV4007947

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5501 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
AlphaMissense	0.5501	ambiguous
REVEL	0.321	indeterminate
SaProt	LLR -8.18	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 142 kb · p 0.7 · regional, not allelic
Overall
CADD	29.3	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 · 1/6,052 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00055% 8/1,453,600 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,052
European (non-Finnish)	0.000595%	168,079

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.Arg26His
Coding: c.77G>A
MANE Select: NM_014772
Type: single nucleotide variant
Location: chr18:48619642 (GRCh38)
Gene constraint: LOEUF 0.487 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 63.13
Residue 26: the 'interaction with ncbp1/cbp80' region

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

Similar variants

CTIF p.Arg26Cys 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-arg26his (accessed [today's date]).

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