Is EFS p.Ser287Arg (c.859A>C) pathogenic?

EFS p.Ser287Arg (c.859A>C) is classified Uncertain significance in EFS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-31). AlphaMissense: ambiguous (0.462); Absent from gnomAD v4.1.

How common is EFS p.Ser287Arg (c.859A>C) in the general population?

EFS p.Ser287Arg (c.859A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFS p.Ser287Arg (c.859A>C)?

AlphaMissense predicts ambiguous (score 0.462) — an in-silico prediction, not a clinical call.

EFS p.Ser287Arg

c.859A>C · rs2502064132 · VCV2473701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.462 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,496,578)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.462	ambiguous
REVEL	0.174	moderately benign-leaning
SaProt	LLR -6.15	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 7,796 bp · p 0.65 · regional, not allelic
Overall
CADD	23.5	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

No allele count reported in gnomAD v4.1 (AN 1,496,578). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EFS
Protein: p.Ser287Arg
Coding: c.859A>C
MANE Select: NM_005864
dbSNP: rs2502064132
Type: single nucleotide variant
Location: chr14:23359619 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.71
Residue 287: the 'disordered' region

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

Similar variants

EFS p.Pro141= Benign ★★ same type
EFS p.Ala167Thr Uncertain significance ★ ⚠ same type
EFS p.Ala186Val Uncertain significance ★ ⚠ same type
EFS p.Ala219Asp Uncertain significance ★ ⚠ same type
EFS p.Ala262Ser Uncertain significance ★ ⚠ same type
EFS p.Ala285Ser Uncertain significance ★ ⚠ same type
EFS p.Ala40Val Uncertain significance ★ ⚠ same type
EFS p.Ala495Pro 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/efs-p-ser287arg (accessed [today's date]).

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