Is EEF2 p.Asp327Glu (c.981C>A) pathogenic?

EEF2 p.Asp327Glu (c.981C>A) is classified Uncertain significance in EEF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: ambiguous (0.498); Very rare (popmax 8.47e-05%, nfe).

How common is EEF2 p.Asp327Glu (c.981C>A) in the general population?

EEF2 p.Asp327Glu (c.981C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about EEF2 p.Asp327Glu (c.981C>A)?

AlphaMissense predicts ambiguous (score 0.498) — an in-silico prediction, not a clinical call.

EEF2 p.Asp327Glu

c.981C>A · rs762204921 · VCV1684705

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.498 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.498	ambiguous
REVEL	0.274	benign-leaning
SaProt	LLR -5.88	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.5	GERP -4.3, phastCons 0.97
Regional constraint	o/e 1.11	unconstrained · MANE · 1,418 bp · p 0.16 · regional, not allelic
Overall
CADD	0.538	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,046 alleles

Overall 6.19e-05% 1/1,614,224 alleles · very rare exomes 1/1,461,858 · genomes 0/152,366 · joint denominator

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.Asp327Glu
Coding: c.981C>A
MANE Select: NM_001961
dbSNP: rs762204921
Type: single nucleotide variant
Location: chr19:3981369 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 327: the tr-type g domain; an α-helix

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

Similar variants

EEF2 p.Asp327Asn Uncertain significance ★ ⚠ same residue
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

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-asp327glu (accessed [today's date]).

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