Is ANKFN1 p.Ser85Arg (c.255T>G) pathogenic?

ANKFN1 p.Ser85Arg (c.255T>G) is classified Uncertain significance in ANKFN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-18). AlphaMissense: likely pathogenic (0.6981); Very rare (popmax 8.48e-05%, nfe).

How common is ANKFN1 p.Ser85Arg (c.255T>G) in the general population?

ANKFN1 p.Ser85Arg (c.255T>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ANKFN1 p.Ser85Arg (c.255T>G)?

AlphaMissense predicts likely pathogenic (score 0.6981) — an in-silico prediction, not a clinical call.

ANKFN1 p.Ser85Arg

c.255T>G · rs747095155 · VCV3120652

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6981 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6981	likely pathogenic
REVEL	0.173	moderately benign-leaning
SaProt	LLR -9.81	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.9	GERP -2.9
Regional constraint	o/e 1.09	unconstrained · MANE · 299 kb · p 0.00097 · regional, not allelic
Overall
CADD	0.251	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S88R vs ClinVar S85R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,844 alleles

Overall 6.84e-05% 1/1,461,608 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: ANKFN1
Protein: p.Ser85Arg
Coding: c.255T>G
MANE Select: NM_001370326
dbSNP: rs747095155
Type: single nucleotide variant
Location: chr17:56350832 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.55

Full ANKFN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKFN1 c.2260+19C>T Uncertain significance ★ ⚠ same type
ANKFN1 c.-73A>G Uncertain significance ★ ⚠ same type
ANKFN1 c.-88G>C Uncertain significance ★ ⚠ same type
ANKFN1 p.Ala24Thr Uncertain significance ★ ⚠ same type
ANKFN1 p.Ala267Val Uncertain significance ★ ⚠ same type
ANKFN1 p.Ala346Ser Uncertain significance ★ same type
ANKFN1 p.Ala361Glu Uncertain significance ★ ⚠ same type
ANKFN1 p.Ala361Thr Uncertain significance ★ ⚠ same type

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/ankfn1-p-ser85arg (accessed [today's date]).

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