Is EEF1A2 p.Thr23Ser (c.67A>T) pathogenic?

EEF1A2 p.Thr23Ser (c.67A>T) is classified Likely benign in EEF1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-22). AlphaMissense: likely pathogenic (0.6286); Ultra-rare (popmax 0.0362%, sas).

How common is EEF1A2 p.Thr23Ser (c.67A>T) in the general population?

EEF1A2 p.Thr23Ser (c.67A>T) is ultra-rare (popmax 0.0362%, sas) (gnomAD).

What do computational predictors say about EEF1A2 p.Thr23Ser (c.67A>T)?

AlphaMissense predicts likely pathogenic (score 0.6286) — an in-silico prediction, not a clinical call.

EEF1A2 p.Thr23Ser

c.67A>T · rs775423668 · VCV515476

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6286 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0362%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6286	likely pathogenic
REVEL	0.146	moderately benign-leaning
SaProt	LLR -11.64	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.18	constrained · MANE · 2,668 bp · p 1.1e-24 · regional, not allelic
Overall
CADD	24.0	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 0.0362% South Asian · 33/91,066 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0231%

Overall 0.00211% 34/1,613,004 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0362%	2,760
Remaining individualsnot grpmax-eligible	0.0016%	62,460

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: EEF1A2
Protein: p.Thr23Ser
Coding: c.67A>T
MANE Select: NM_001958
dbSNP: rs775423668
Type: single nucleotide variant
Location: chr20:63497697 (GRCh38)
Gene constraint: LOEUF 0.314 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.70 · 2 PDB
Residue 23: the tr-type g domain; an α-helix

Full EEF1A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEF1A2 p.Arg266Gln Likely pathogenic ★★ same type
EEF1A2 p.Arg266Trp Pathogenic/Likely pathogenic ★★ same type
EEF1A2 p.Arg423Cys Pathogenic/Likely pathogenic ★★ same type
EEF1A2 p.Arg69Cys Pathogenic ★★ same type
EEF1A2 p.Asp252Asn Pathogenic/Likely pathogenic ★★ ⚠ same type
EEF1A2 p.Asp91Asn Pathogenic ★★ same type
EEF1A2 p.Asp97Asn Pathogenic/Likely pathogenic ★★ same type
EEF1A2 p.Glu122Lys Pathogenic/Likely pathogenic ★★ 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/eef1a2-p-thr23ser (accessed [today's date]).

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