Is CFI p.Asp211Tyr (c.631G>T) pathogenic?

CFI p.Asp211Tyr (c.631G>T) is classified Uncertain significance in CFI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-10). AlphaMissense: likely benign (0.1489); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CFI p.Asp211Tyr (c.631G>T)?

CFI p.Asp211Tyr (c.631G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CFI p.Asp211Tyr (c.631G>T) in the general population?

CFI p.Asp211Tyr (c.631G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFI p.Asp211Tyr (c.631G>T)?

AlphaMissense predicts likely benign (score 0.1489) — an in-silico prediction, not a clinical call.

CFI p.Asp211Tyr

c.631G>T · VCV4614274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1489 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1489	likely benign
REVEL	0.165	moderately benign-leaning
SaProt	LLR -3.98	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 -0.38	GERP -2.3
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic
Overall
CADD	19.19	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFI
Protein: p.Asp211Tyr
Coding: c.631G>T
MANE Select: NM_000204
Type: single nucleotide variant
Location: chr4:109761544 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 211: a disulfide bond; the srcr domain; a β-strand

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.Asp211= Likely benign ★ same residue
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

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-asp211tyr (accessed [today's date]).

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