Is EEFSEC p.Ala435Val (c.1304C>T) pathogenic?

EEFSEC p.Ala435Val (c.1304C>T) is classified Benign in EEFSEC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-24). AlphaMissense: likely benign (0.0948); Low-frequency (popmax 4.85%, afr).

How common is EEFSEC p.Ala435Val (c.1304C>T) in the general population?

EEFSEC p.Ala435Val (c.1304C>T) is low-frequency (popmax 4.85%, afr) (gnomAD).

What do computational predictors say about EEFSEC p.Ala435Val (c.1304C>T)?

AlphaMissense predicts likely benign (score 0.0948) — an in-silico prediction, not a clinical call.

EEFSEC p.Ala435Val

c.1304C>T · rs34326479 · VCV785062

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0948 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.85%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0948	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -6.67	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 0.18, phastCons 0.009
Regional constraint	o/e 0.93	unconstrained · MANE · 255 kb · p 0.039 · regional, not allelic
Overall
CADD	15.27	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 4.85% African / African-American · 3,643/75,042 alleles

Filtering AF 4.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.67%

Overall 0.27% 4,364/1,614,086 alleles · low-frequency exomes 2,094/1,461,778 · genomes 2,270/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.85%	21
Admixed American	0.508%	197
Remaining individualsnot grpmax-eligible	0.357%	280
Middle Eastern	0.165%	606
European (non-Finnish)	0.0143%	6,982
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401
South Asian	0.00659%	15,180
Finnishnot grpmax-eligible	0.00469%	21,309
East Asian	0.00223%	44,890

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.Ala435Val
Coding: c.1304C>T
MANE Select: NM_021937
dbSNP: rs34326479
Type: single nucleotide variant
Location: chr3:128341750 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.98 · 4 PDB
Residue 435: a UniProt-annotated variant site (in nedpsb; likely pathogenic; decreased selenocysteine incorporation in selenoproteins); a UniProt-annotated variant site (in)

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

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.Phe581Cys Benign ★★ same type
EEFSEC p.Pro180= Benign ★★ same type
EEFSEC p.Asp390Ala Likely pathogenic ★ ⚠ 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-ala435val (accessed [today's date]).

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