Is CFAP418 p.Ser85Phe (c.254C>T) pathogenic?

CFAP418 p.Ser85Phe (c.254C>T) is classified Uncertain significance in CFAP418 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2022-10-25). AlphaMissense: likely benign (0.1284); Ultra-rare (popmax 0.0549%, amr); Associated with cone-rod dystrophy 16.

What condition is associated with CFAP418 p.Ser85Phe (c.254C>T)?

CFAP418 p.Ser85Phe (c.254C>T) is associated with cone-rod dystrophy 16, retinitis pigmentosa, bardet-biedl syndrome 21 (ClinVar).

How common is CFAP418 p.Ser85Phe (c.254C>T) in the general population?

CFAP418 p.Ser85Phe (c.254C>T) is ultra-rare (popmax 0.0549%, amr) (gnomAD).

How is Cone rod dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CFAP418 p.Ser85Phe (c.254C>T)?

AlphaMissense predicts likely benign (score 0.1284) — an in-silico prediction, not a clinical call.

CFAP418 p.Ser85Phe

c.254C>T · rs764463463 · VCV1681133

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1284 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0549%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cone-rod dystrophy 16

Computational evidence

Protein change
AlphaMissense	0.1284	likely benign
REVEL	0.367	indeterminate
SaProt	LLR -9.12	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.47	acceptor gain · deltas
Pangolin	Δ0.25	gain · loss 0.12 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 22 kb · p 0.91 · regional, not allelic
Overall
CADD	24.4	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 0.0549% Admixed American · 28/50,974 alleles

Filtering AF 0.039% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0336%

Overall 0.00196% 31/1,580,602 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0549%	1,820
Remaining individualsnot grpmax-eligible	0.0049%	20,390

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.Ser85Phe
Coding: c.254C>T
MANE Select: NM_177965
dbSNP: rs764463463
Type: single nucleotide variant
Location: chr8:95260522 (GRCh38)
Gene constraint: LOEUF 1.642 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.73

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

Disease context

cone-rod dystrophy 16 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa bardet-biedl syndrome 21

For Cone rod dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CFAP418 p.Ser85Pro Uncertain significance ★ ⚠ same residue
CFAP418 p.Arg177Trp Pathogenic/Likely pathogenic ★★ same condition
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.Arg177Gln 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-ser85phe (accessed [today's date]).

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