Is CFI p.Ala163Val (c.488C>T) pathogenic?

CFI p.Ala163Val (c.488C>T) is classified Uncertain significance in CFI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely benign (0.2486); Very rare (popmax 0.00034%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CFI p.Ala163Val (c.488C>T)?

CFI p.Ala163Val (c.488C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CFI p.Ala163Val (c.488C>T) in the general population?

CFI p.Ala163Val (c.488C>T) is very rare (popmax 0.00034%, nfe) (gnomAD).

What do computational predictors say about CFI p.Ala163Val (c.488C>T)?

AlphaMissense predicts likely benign (score 0.2486) — an in-silico prediction, not a clinical call.

CFI p.Ala163Val

c.488C>T · rs1458125413 · VCV3143838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2486 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2486	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -7.39	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 7.2	GERP 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic
Overall
CADD	23.7	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 0.00034% European (non-Finnish) · 4/1,176,216 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000249% 4/1,609,292 alleles · very 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: CFI
Protein: p.Ala163Val
Coding: c.488C>T
MANE Select: NM_000204
dbSNP: rs1458125413
Type: single nucleotide variant
Location: chr4:109761687 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 163: a disulfide bond; the srcr domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFI p.Ala511Val Uncertain significance ★★ ⚠ same condition
CFI p.Asn102Ser Uncertain significance ★★ ⚠ same condition
CFI p.Glu109Lys Uncertain significance ★★ ⚠ same condition
CFI p.Glu445Asp Uncertain significance ★★ ⚠ same condition
CFI p.His401Gln Uncertain significance ★★ ⚠ same condition
CFI p.Ile126Thr Uncertain significance ★★ ⚠ same condition
CFI p.Leu491Arg Uncertain significance ★★ ⚠ same condition
CFI p.Lys69Glu Uncertain significance ★★ ⚠ same condition

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/cfi-p-ala163val (accessed [today's date]).

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