Is EARS2 p.Asn365Ser (c.1094A>G) pathogenic?

EARS2 p.Asn365Ser (c.1094A>G) is classified Likely benign in EARS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). AlphaMissense: likely benign (0.0566); Very rare (popmax 0.00769%, sas); Associated with Inborn genetic diseases.

What condition is associated with EARS2 p.Asn365Ser (c.1094A>G)?

EARS2 p.Asn365Ser (c.1094A>G) is associated with Inborn genetic diseases (ClinVar).

How common is EARS2 p.Asn365Ser (c.1094A>G) in the general population?

EARS2 p.Asn365Ser (c.1094A>G) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about EARS2 p.Asn365Ser (c.1094A>G)?

AlphaMissense predicts likely benign (score 0.0566) — an in-silico prediction, not a clinical call.

EARS2 p.Asn365Ser

c.1094A>G · rs779506316 · VCV2343779

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0566 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0566	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -5.95	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 -2.8	GERP -0.84
Regional constraint	o/e 0.94	unconstrained · MANE · 11 kb · p 0.22 · regional, not allelic
Overall
CADD	0.507	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 0.00769% South Asian · 7/91,082 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000616% 9/1,461,878 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,012
European (non-Finnish)	0.000169%	590,019

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: EARS2
Protein: p.Asn365Ser
Coding: c.1094A>G
MANE Select: NM_001083614
dbSNP: rs779506316
Type: single nucleotide variant
Location: chr16:23529871 (GRCh38)
Gene constraint: LOEUF 1.138 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.84

Full EARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EARS2 p.Ala263Thr Uncertain significance ★★ ⚠ same condition
EARS2 p.Ala299Val Uncertain significance ★★ ⚠ same condition
EARS2 p.Arg11Ser Uncertain significance ★★ ⚠ same condition
EARS2 p.Arg156Trp Uncertain significance ★★ ⚠ same condition
EARS2 p.Arg166Gln Uncertain significance ★★ ⚠ same condition
EARS2 p.Arg514Trp Uncertain significance ★★ ⚠ same condition
EARS2 p.Arg55Cys Uncertain significance ★★ ⚠ same condition
EARS2 p.Asp182Gly Uncertain significance ★★ ⚠ same condition

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/ears2-p-asn365ser (accessed [today's date]).

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