Is ERCC4 p.Asn244Lys (c.732C>G) pathogenic?

ERCC4 p.Asn244Lys (c.732C>G) is classified Uncertain significance in ERCC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely pathogenic (0.9086); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ERCC4 p.Asn244Lys (c.732C>G)?

ERCC4 p.Asn244Lys (c.732C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ERCC4 p.Asn244Lys (c.732C>G) in the general population?

ERCC4 p.Asn244Lys (c.732C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERCC4 p.Asn244Lys (c.732C>G)?

AlphaMissense predicts likely pathogenic (score 0.9086) — an in-silico prediction, not a clinical call.

ERCC4 p.Asn244Lys

c.732C>G · rs1386569359 · VCV2476324

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9086 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9086	likely pathogenic
REVEL	0.414	indeterminate
SaProt	LLR -11.17	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 0.41	GERP -0.82, phastCons 0.99
Regional constraint	o/e 1.08	unconstrained · MANE · 28 kb · p 0.011 · regional, not allelic
Overall
CADD	21.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ERCC4
Protein: p.Asn244Lys
Coding: c.732C>G
MANE Select: NM_005236
dbSNP: rs1386569359
Type: single nucleotide variant
Location: chr16:13928175 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 13 PDB
Residue 244: the 'helicase-like' region; the 'leucine-zipper 1' region

Full ERCC4 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

ERCC4 p.Asn244His Uncertain significance ★ ⚠ same residue
ERCC4 p.Ala874Thr Uncertain significance ★★ ⚠ same condition
ERCC4 p.Arg158His Uncertain significance ★★ ⚠ same condition
ERCC4 p.Arg598Lys Uncertain significance ★★ ⚠ same condition
ERCC4 p.Arg618His Uncertain significance ★★ ⚠ same condition
ERCC4 p.Arg864Cys Uncertain significance ★★ ⚠ same condition
ERCC4 p.Arg9Gly Uncertain significance ★★ ⚠ same condition
ERCC4 p.Asp664Tyr 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/ercc4-p-asn244lys (accessed [today's date]).

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