Is CFAP418 p.Arg177Trp (c.529C>T) pathogenic?

CFAP418 p.Arg177Trp (c.529C>T) is classified Pathogenic/Likely pathogenic in CFAP418 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-05-14). AlphaMissense: likely pathogenic (0.7253); Ultra-rare (popmax 0.0165%, mid); Associated with C8ORF37 & CFAP418-related disorders.

What condition is associated with CFAP418 p.Arg177Trp (c.529C>T)?

CFAP418 p.Arg177Trp (c.529C>T) is associated with C8ORF37 & CFAP418-related disorders, cone-rod dystrophy 16, inherited retinal dystrophy (ClinVar).

How common is CFAP418 p.Arg177Trp (c.529C>T) in the general population?

CFAP418 p.Arg177Trp (c.529C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CFAP418 p.Arg177Trp (c.529C>T)?

AlphaMissense predicts likely pathogenic (score 0.7253) — an in-silico prediction, not a clinical call.

CFAP418 p.Arg177Trp

c.529C>T · rs387907136 · VCV31194

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.7253 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

C8ORF37 & CFAP418-related disorders

Computational evidence

Protein change
AlphaMissense	0.7253	likely pathogenic ✓ concordant with ClinVar
REVEL	0.848	moderately pathogenic-leaning
SaProt	LLR -14.59	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 22 kb · p 0.91 · 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 · 1/6,078 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00236% 38/1,613,454 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,078
South Asian	0.00659%	15,170
Admixed American	0.00334%	29,965
European (non-Finnish)	0.00246%	40,685

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.Arg177Trp
Coding: c.529C>T
MANE Select: NM_177965
dbSNP: rs387907136
Type: single nucleotide variant
Location: chr8:95247712 (GRCh38)
Gene constraint: LOEUF 1.642 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.73
Residue 177: a UniProt-annotated variant site (in cord16 and bbs21; does not affect interaction with fam161a)

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

Disease context

C8ORF37 & CFAP418-related disorders

Also linked: cone-rod dystrophy 16 inherited retinal dystrophy retinitis pigmentosa bardet-biedl syndrome 21

Similar variants

CFAP418 p.Arg177Gln Uncertain significance ★★ ⚠ same residue
CFAP418 p.Arg177Pro Uncertain significance ★ ⚠ same residue
CFAP418 p.Trp147Ter Pathogenic/Likely pathogenic ★★ same condition
CFAP418 c.*408G>A Uncertain significance ★★ same condition
CFAP418 c.*965C>G Uncertain significance ★★ same condition
CFAP418 p.Ala178Val Uncertain significance ★★ ⚠ same condition
CFAP418 p.Ala45Gly Uncertain significance ★★ ⚠ same condition
CFAP418 p.Arg186Gly 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-arg177trp (accessed [today's date]).

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