Is CFAP418 p.Leu71Phe (c.211C>T) pathogenic?

CFAP418 p.Leu71Phe (c.211C>T) is classified Uncertain significance in CFAP418 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-01). AlphaMissense: likely benign (0.0193); Ultra-rare (popmax 0.0147%, afr); Associated with inherited retinal dystrophy.

What condition is associated with CFAP418 p.Leu71Phe (c.211C>T)?

CFAP418 p.Leu71Phe (c.211C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is CFAP418 p.Leu71Phe (c.211C>T) in the general population?

CFAP418 p.Leu71Phe (c.211C>T) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about CFAP418 p.Leu71Phe (c.211C>T)?

AlphaMissense predicts likely benign (score 0.0193) — an in-silico prediction, not a clinical call.

CFAP418 p.Leu71Phe

c.211C>T · rs145542989 · VCV967954

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0193 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.0193	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -10.64	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 0.63, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 22 kb · p 0.91 · regional, not allelic
Overall
CADD	16.53	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 0.0147% African / African-American · 11/74,764 alleles

Filtering AF 0.00817% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.000746% 12/1,608,270 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,797
East Asian	0.00224%	44,704

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: CFAP418
Protein: p.Leu71Phe
Coding: c.211C>T
MANE Select: NM_177965
dbSNP: rs145542989
Type: single nucleotide variant
Location: chr8:95263719 (GRCh38)
Gene constraint: LOEUF 1.642 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.73
Residue 71: the 'required for interaction with fam161a' region

Full CFAP418 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP418 p.Arg177Trp Pathogenic/Likely pathogenic ★★ same condition
CFAP418 p.Trp147Ter Pathogenic/Likely pathogenic ★★ same condition
CFAP418 p.Glu13Lys Uncertain significance ★★ ⚠ same condition
CFAP418 p.Pro106Leu Uncertain significance ★★ ⚠ same condition
CFAP418 p.Ile188= Likely benign ★★ same condition
CFAP418 p.Pro19Ala Benign/Likely benign ★★ ⚠ same condition
CFAP418 c.374+1G>A Likely pathogenic ★ same condition
CFAP418 p.Arg157= 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/cfap418-p-leu71phe (accessed [today's date]).

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