Is ARF5 p.Ser137Arg (c.411C>A) pathogenic?

ARF5 p.Ser137Arg (c.411C>A) is classified Uncertain significance in ARF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-05). AlphaMissense: likely pathogenic (0.7474); Absent from gnomAD v4.1.

How common is ARF5 p.Ser137Arg (c.411C>A) in the general population?

ARF5 p.Ser137Arg (c.411C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARF5 p.Ser137Arg (c.411C>A)?

AlphaMissense predicts likely pathogenic (score 0.7474) — an in-silico prediction, not a clinical call.

ARF5 p.Ser137Arg

c.411C>A · rs775287559 · VCV2299669

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7474 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7474	likely pathogenic
REVEL	0.229	benign-leaning
SaProt	LLR -8.73	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.88 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.9	GERP -5.5
Regional constraint	o/e 0.63	unconstrained · MANE · 1,780 bp · p 3.4e-06 · regional, not allelic
Overall
CADD	19.79	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

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: ARF5
Protein: p.Ser137Arg
Coding: c.411C>A
MANE Select: NM_001662
dbSNP: rs775287559
Type: single nucleotide variant
Location: chr7:127591043 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.35 (gnomAD)
Structure: AlphaFold pLDDT 86.31 · 1 PDB
Residue 137: an α-helix

Full ARF5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARF5 p.Thr164= Benign ★★ same type
ARF5 p.Arg149Cys Uncertain significance ★ ⚠ same type
ARF5 p.Arg151Cys Uncertain significance ★ ⚠ same type
ARF5 p.Arg180Cys Uncertain significance ★ same type
ARF5 p.Arg97Trp Uncertain significance ★ ⚠ same type
ARF5 p.Asp114Asn Uncertain significance ★ same type
ARF5 p.Gln112Ter Uncertain significance ★ same type
ARF5 p.Glu138Gln 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/arf5-p-ser137arg (accessed [today's date]).

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