Is EML5 p.Arg464Ser (c.1392A>C) pathogenic?

EML5 p.Arg464Ser (c.1392A>C) is classified Uncertain significance in EML5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: ambiguous (0.3591); Absent from gnomAD v4.1.

How common is EML5 p.Arg464Ser (c.1392A>C) in the general population?

EML5 p.Arg464Ser (c.1392A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EML5 p.Arg464Ser (c.1392A>C)?

AlphaMissense predicts ambiguous (score 0.3591) — an in-silico prediction, not a clinical call.

EML5 p.Arg464Ser

c.1392A>C · rs2545358203 · VCV3088698

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3591 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3591	ambiguous
REVEL	0.094	moderately benign-leaning
SaProt	LLR -7.83	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.92 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 113 kb · p 6.7e-08 · regional, not allelic
Overall
CADD	21.7	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: EML5
Protein: p.Arg464Ser
Coding: c.1392A>C
MANE Select: NM_183387
dbSNP: rs2545358203
Type: single nucleotide variant
Location: chr14:88714991 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.18

Full EML5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EML5 p.Ala1787Glu Benign ★★ same type
EML5 p.Thr194Met Benign ★★ same type
EML5 p.Val1361= Benign ★★ same type
EML5 p.Ala1575Thr Uncertain significance ★ ⚠ same type
EML5 p.Ala1606Val Uncertain significance ★ ⚠ same type
EML5 p.Ala1615Val Uncertain significance ★ ⚠ same type
EML5 p.Ala1746Val Uncertain significance ★ ⚠ same type
EML5 p.Ala1787Ser 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/eml5-p-arg464ser (accessed [today's date]).

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