Is GRHL2 p.Ser210Arg (c.630C>A) pathogenic?

GRHL2 p.Ser210Arg (c.630C>A) is classified Uncertain significance in GRHL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely pathogenic (0.9105); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GRHL2 p.Ser210Arg (c.630C>A)?

GRHL2 p.Ser210Arg (c.630C>A) is associated with Inborn genetic diseases (ClinVar).

How common is GRHL2 p.Ser210Arg (c.630C>A) in the general population?

GRHL2 p.Ser210Arg (c.630C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRHL2 p.Ser210Arg (c.630C>A)?

AlphaMissense predicts likely pathogenic (score 0.9105) — an in-silico prediction, not a clinical call.

GRHL2 p.Ser210Arg

c.630C>A · rs1811541408 · VCV3102291

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9105 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9105	likely pathogenic
REVEL	0.215	benign-leaning
SaProt	LLR -8.59	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.5, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 30 kb · p 0.92 · regional, not allelic
Overall
CADD	19.63	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

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: GRHL2
Protein: p.Ser210Arg
Coding: c.630C>A
MANE Select: NM_024915
dbSNP: rs1811541408
Type: single nucleotide variant
Location: chr8:101558764 (GRCh38)
Gene constraint: LOEUF 0.367 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.46 · 1 PDB

Full GRHL2 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

GRHL2 p.Ala46Thr Uncertain significance ★★ ⚠ same condition
GRHL2 p.Arg229Gln Uncertain significance ★★ ⚠ same condition
GRHL2 p.Arg290Leu Uncertain significance ★★ ⚠ same condition
GRHL2 p.Arg401His Uncertain significance ★★ ⚠ same condition
GRHL2 p.Arg434Ser Uncertain significance ★★ ⚠ same condition
GRHL2 p.Arg513Gln Uncertain significance ★★ ⚠ same condition
GRHL2 p.Ile369Val Uncertain significance ★★ ⚠ same condition
GRHL2 p.Leu107Met 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/grhl2-p-ser210arg (accessed [today's date]).

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