Is EEFSEC p.Asp390Ala (c.1169A>C) pathogenic?

EEFSEC p.Asp390Ala (c.1169A>C) is classified Likely pathogenic in EEFSEC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). AlphaMissense: likely benign (0.0642); Ultra-rare (popmax 0.033%, mid); Associated with autosomal recessive non-syndromic intellectual disability.

What condition is associated with EEFSEC p.Asp390Ala (c.1169A>C)?

EEFSEC p.Asp390Ala (c.1169A>C) is associated with autosomal recessive non-syndromic intellectual disability (ClinVar).

How common is EEFSEC p.Asp390Ala (c.1169A>C) in the general population?

EEFSEC p.Asp390Ala (c.1169A>C) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about EEFSEC p.Asp390Ala (c.1169A>C)?

AlphaMissense predicts likely benign (score 0.0642) — an in-silico prediction, not a clinical call.

EEFSEC p.Asp390Ala

c.1169A>C · rs1171115208 · VCV3067138

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0642 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive non-syndromic intellectual disability

Computational evidence

Protein change
AlphaMissense	0.0642	likely benign ⚠ discordant with ClinVar
REVEL	0.07	moderately benign-leaning
SaProt	LLR -5.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -0.39, phastCons 0.99
Regional constraint	o/e 0.93	unconstrained · MANE · 255 kb · p 0.039 · regional, not allelic
Overall
CADD	12.52	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000616% 9/1,461,708 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.008%	12,502
European (non-Finnish)	0.000169%	590,023

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: EEFSEC
Protein: p.Asp390Ala
Coding: c.1169A>C
MANE Select: NM_021937
dbSNP: rs1171115208
Type: single nucleotide variant
Location: chr3:128341615 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.98 · 4 PDB
Residue 390: a UniProt-annotated variant site (in nedpsb; likely pathogenic; decreased selenocysteine incorporation in selenoproteins)

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

Disease context

autosomal recessive non-syndromic intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EEFSEC p.Arg285Gln Uncertain significance ★★ ⚠ same type
EEFSEC p.Arg424Gln Uncertain significance ★★ ⚠ same type
EEFSEC p.Phe463Leu Uncertain significance ★★ ⚠ same type
EEFSEC p.Ala435Val Benign ★★ same type
EEFSEC p.Phe581Cys Benign ★★ same type
EEFSEC p.Pro180= Benign ★★ same type
EEFSEC p.Glu514Ter Likely pathogenic ★ same type
EEFSEC p.Ala193Ser 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/eefsec-p-asp390ala (accessed [today's date]).

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