Is EEF2 p.Asn673Ser (c.2018A>G) pathogenic?

EEF2 p.Asn673Ser (c.2018A>G) is classified Uncertain significance in EEF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-29). AlphaMissense: likely benign (0.1043); Ultra-rare (popmax 0.0117%, amr).

How common is EEF2 p.Asn673Ser (c.2018A>G) in the general population?

EEF2 p.Asn673Ser (c.2018A>G) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about EEF2 p.Asn673Ser (c.2018A>G)?

AlphaMissense predicts likely benign (score 0.1043) — an in-silico prediction, not a clinical call.

EEF2 p.Asn673Ser

c.2018A>G · rs144336814 · VCV2971631

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1043 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1043	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -10.88	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 1.3, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 1,578 bp · p 7.1e-09 · regional, not allelic
Overall
CADD	21.5	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

Grpmax group 0.0117% Admixed American · 7/59,866 alleles

Filtering AF 0.00545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00223% 36/1,611,048 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,552
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,556
Remaining individualsnot grpmax-eligible	0.00321%	31,192
European (non-Finnish)	0.00212%	47,130
South Asian	0.0011%	90,858

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.Asn673Ser
Coding: c.2018A>G
MANE Select: NM_001961
dbSNP: rs144336814
Type: single nucleotide variant
Location: chr19:3977868 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 673: an α-helix

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

Similar variants

EEF2 p.Asn673= Likely benign ★ 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-asn673ser (accessed [today's date]).

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