Is EIF3A p.Arg970His (c.2909G>A) pathogenic?

EIF3A p.Arg970His (c.2909G>A) is classified Uncertain significance in EIF3A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely benign (0.1595); Ultra-rare (popmax 0.0132%, sas).

How common is EIF3A p.Arg970His (c.2909G>A) in the general population?

EIF3A p.Arg970His (c.2909G>A) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

What do computational predictors say about EIF3A p.Arg970His (c.2909G>A)?

AlphaMissense predicts likely benign (score 0.1595) — an in-silico prediction, not a clinical call.

EIF3A p.Arg970His

c.2909G>A · VCV4017151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1595 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1595	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -13.26	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 14 kb · p 0.0035 · regional, not allelic
Overall
CADD	31.0	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 0.0132% South Asian · 12/91,080 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.000805% 13/1,614,184 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,590
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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: EIF3A
Protein: p.Arg970His
Coding: c.2909G>A
MANE Select: NM_003750
Type: single nucleotide variant
Location: chr10:119042611 (GRCh38)
Gene constraint: LOEUF 0.18 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.62 · 30 PDB
Residue 970: the 'disordered' region; the '25 x 10 aa approximate tandem repeats of [de]-[de]-[de]-r-[sevgfpilv]-[hpsn]-[rsw]-[rl]-[drgtihn]-[epmanlgdt]' region

Full EIF3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF3A p.Arg970Cys Uncertain significance ★ ⚠ same residue
EIF3A p.Ala1358= Benign ★★ same type
EIF3A p.Arg1046Trp Likely benign ★★ ⚠ same type
EIF3A p.Arg406= Benign/Likely benign ★★ same type
EIF3A p.Arg803Lys Benign ★★ ⚠ same type
EIF3A p.Asp993Glu Benign ★★ ⚠ same type
EIF3A p.Arg1273Ser Likely pathogenic ★ ⚠ same type
EIF3A p.Ala1354Ser 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/eif3a-p-arg970his (accessed [today's date]).

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