Is EARS2 p.Val244Met (c.730G>A) pathogenic?

EARS2 p.Val244Met (c.730G>A) is classified Uncertain significance in EARS2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-01). AlphaMissense: likely pathogenic (0.8404); Very rare (popmax 0.00935%, afr); Associated with Inborn genetic diseases.

What condition is associated with EARS2 p.Val244Met (c.730G>A)?

EARS2 p.Val244Met (c.730G>A) is associated with Inborn genetic diseases (ClinVar).

How common is EARS2 p.Val244Met (c.730G>A) in the general population?

EARS2 p.Val244Met (c.730G>A) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about EARS2 p.Val244Met (c.730G>A)?

AlphaMissense predicts likely pathogenic (score 0.8404) — an in-silico prediction, not a clinical call.

EARS2 p.Val244Met

c.730G>A · rs769256010 · VCV1697076

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8404 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8404	likely pathogenic
REVEL	0.5	indeterminate
SaProt	LLR -12.81	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 11 kb · p 0.22 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,862 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00143% 23/1,611,626 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,695
Remaining individualsnot grpmax-eligible	0.0016%	62,338
European (non-Finnish)	0.00127%	78,619

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.Val244Met
Coding: c.730G>A
MANE Select: NM_001083614
dbSNP: rs769256010
Type: single nucleotide variant
Location: chr16:23535116 (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-val244met (accessed [today's date]).

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