Is EEF2 p.Ala511Ser (c.1531G>T) pathogenic?

EEF2 p.Ala511Ser (c.1531G>T) is classified Uncertain significance in EEF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-24). AlphaMissense: likely benign (0.3226); Very rare (popmax 0.000763%, nfe).

How common is EEF2 p.Ala511Ser (c.1531G>T) in the general population?

EEF2 p.Ala511Ser (c.1531G>T) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about EEF2 p.Ala511Ser (c.1531G>T)?

AlphaMissense predicts likely benign (score 0.3226) — an in-silico prediction, not a clinical call.

EEF2 p.Ala511Ser

c.1531G>T · rs1308649928 · VCV2637434

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3226 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3226	likely benign
REVEL	0.362	indeterminate
SaProt	LLR -9.96	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 657 bp · p 1.6e-07 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.000763% European (non-Finnish) · 9/1,180,046 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000616% 9/1,461,456 alleles · very rare

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.Ala511Ser
Coding: c.1531G>T
MANE Select: NM_001961
dbSNP: rs1308649928
Type: single nucleotide variant
Location: chr19:3979882 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 511: 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-ala511ser (accessed [today's date]).

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