Is EARS2 p.Ser70Asn (c.209G>A) pathogenic?

EARS2 p.Ser70Asn (c.209G>A) is classified Conflicting classifications of pathogenicity in EARS2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-09-20). AlphaMissense: likely benign (0.1381); Ultra-rare (popmax 0.0423%, eas); Associated with Inborn genetic diseases.

What condition is associated with EARS2 p.Ser70Asn (c.209G>A)?

EARS2 p.Ser70Asn (c.209G>A) is associated with Inborn genetic diseases (ClinVar).

How common is EARS2 p.Ser70Asn (c.209G>A) in the general population?

EARS2 p.Ser70Asn (c.209G>A) is ultra-rare (popmax 0.0423%, eas) (gnomAD).

What do computational predictors say about EARS2 p.Ser70Asn (c.209G>A)?

AlphaMissense predicts likely benign (score 0.1381) — an in-silico prediction, not a clinical call.

EARS2 p.Ser70Asn

c.209G>A · rs201941745 · VCV2600739

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1381 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0423%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1381	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -9.55	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 1	GERP 1.7, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 22 kb · p 0.014 · regional, not allelic
Overall
CADD	21.0	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 0.0423% East Asian · 19/44,888 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.023%

Overall 0.00149% 24/1,614,214 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0423%	2,363
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.000339%	295,006

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.Ser70Asn
Coding: c.209G>A
MANE Select: NM_001083614
dbSNP: rs201941745
Type: single nucleotide variant
Location: chr16:23552235 (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.Ser70Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-ser70asn (accessed [today's date]).

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