Is EFTUD2 p.Ser212Pro (c.634T>C) pathogenic?

EFTUD2 p.Ser212Pro (c.634T>C) is classified Uncertain significance in EFTUD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-03). AlphaMissense: likely pathogenic (0.9544); Very rare (popmax 0.00333%, amr).

How common is EFTUD2 p.Ser212Pro (c.634T>C) in the general population?

EFTUD2 p.Ser212Pro (c.634T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about EFTUD2 p.Ser212Pro (c.634T>C)?

AlphaMissense predicts likely pathogenic (score 0.9544) — an in-silico prediction, not a clinical call.

EFTUD2 p.Ser212Pro

c.634T>C · rs1417067254 · VCV2723145

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9544 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9544	likely pathogenic
REVEL	0.885	moderately pathogenic-leaning
SaProt	LLR -12.26	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 19 kb · p 1.7e-08 · regional, not allelic
Overall
CADD	29.7	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 0.00333% Admixed American · 2/60,014 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000274% 4/1,461,688 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,007
European (non-Finnish)	0.000169%	589,974

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: EFTUD2
Protein: p.Ser212Pro
Coding: c.634T>C
MANE Select: NM_004247
dbSNP: rs1417067254
Type: single nucleotide variant
Location: chr17:44879624 (GRCh38)
Gene constraint: LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 89.94 · 72 PDB
Residue 212: the tr-type g domain; an α-helix

Full EFTUD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFTUD2 p.Ser212Cys Uncertain significance ★ ⚠ same residue
EFTUD2 c.1058+1G>A Pathogenic ★★ same type
EFTUD2 c.1414-2A>G Pathogenic/Likely pathogenic ★★ same type
EFTUD2 c.1607+1G>T Likely pathogenic ★★ same type
EFTUD2 c.1962+1G>A Pathogenic/Likely pathogenic ★★ same type
EFTUD2 c.2133-2A>G Pathogenic/Likely pathogenic ★★ same type
EFTUD2 c.2562-2A>G Pathogenic/Likely pathogenic ★★ same type
EFTUD2 c.702+1G>T 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/eftud2-p-ser212pro (accessed [today's date]).

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