Is EEF2 p.Arg580Cys (c.1738C>T) pathogenic?

EEF2 p.Arg580Cys (c.1738C>T) is classified Uncertain significance in EEF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-18). AlphaMissense: likely pathogenic (0.8231); Very rare (popmax 0.00147%, sas).

How common is EEF2 p.Arg580Cys (c.1738C>T) in the general population?

EEF2 p.Arg580Cys (c.1738C>T) is very rare (popmax 0.00147%, sas) (gnomAD).

What do computational predictors say about EEF2 p.Arg580Cys (c.1738C>T)?

AlphaMissense predicts likely pathogenic (score 0.8231) — an in-silico prediction, not a clinical call.

EEF2 p.Arg580Cys

c.1738C>T · VCV3571833

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8231 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00147%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8231	likely pathogenic
REVEL	0.378	indeterminate
SaProt	LLR -12.12	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.71 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.12	constrained · MANE · 1,197 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00147% South Asian · 1/68,042 alleles

Filtering AF 0.000661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000509%

Overall 0.00117% 17/1,455,786 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00433%	23,080
Remaining individualsnot grpmax-eligible	0.00357%	27,974
South Asiangrpmax	0.00147%	68,042
European (non-Finnish)	0.00118%	84,422

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: EEF2
Protein: p.Arg580Cys
Coding: c.1738C>T
MANE Select: NM_001961
Type: single nucleotide variant
Location: chr19:3978148 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 580: a β-strand

Full EEF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEF2 p.Ala237Thr Uncertain significance ★★ ⚠ same type
EEF2 p.Ala238Thr Uncertain significance ★★ ⚠ same type
EEF2 p.Ala338Gly Uncertain significance ★★ ⚠ same type
EEF2 p.Ala624Thr Uncertain significance ★★ ⚠ same type
EEF2 p.Ala808Val Uncertain significance ★★ ⚠ same type
EEF2 p.Arg633His Uncertain significance ★★ ⚠ same type
EEF2 p.Arg647His Uncertain significance ★★ ⚠ same type
EEF2 p.Arg726Trp 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/eef2-p-arg580cys (accessed [today's date]).

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