Is KERA p.Val23= (c.69G>A) pathogenic?

KERA p.Val23= (c.69G>A) is classified Benign in KERA (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Common (popmax 78.8%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with cornea plana 2.

What condition is associated with KERA p.Val23= (c.69G>A)?

KERA p.Val23= (c.69G>A) is associated with cornea plana 2 (ClinVar).

KERA p.Val23=

Q: How common is KERA p.Val23= (c.69G>A) in the general population?

KERA p.Val23= (c.69G>A) is common (popmax 78.8%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.69G>A · rs2735333 · VCV1174695

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 78.8%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

cornea plana 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.59	GERP 0.27, phastCons 1
Overall
CADD	6.716	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 78.8% European (non-Finnish) · 927,456/1,176,836 alleles

Filtering AF 78.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 78.6%

Overall 75.9% 1,221,487/1,609,058 alleles · common exomes 1,123,059/1,458,120 · genomes 98,428/150,938 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	82.4%	1
European (non-Finnish)grpmax	78.8%	1
East Asian	78.3%	1
Remaining individualsnot grpmax-eligible	75.6%	1
Ashkenazi Jewishnot grpmax-eligible	75.2%	1
South Asian	74.1%	1
Middle Eastern	73.9%	1
Amishnot grpmax-eligible	68%	1
Admixed American	67%	1
African / African-American	33.4%	3

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: KERA
Protein: p.Val23=
Coding: c.69G>A
MANE Select: NM_007035
dbSNP: rs2735333
Type: single nucleotide variant
Location: chr12:91056213 (GRCh38)
Gene constraint: LOEUF 1.284 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.42

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

Disease context

cornea plana 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KERA p.Arg279Ter Pathogenic ★★ same condition
KERA p.Asn247Ser Pathogenic ★★ same condition
KERA p.Arg313Ter Pathogenic ★ same condition
KERA p.Asn176Lys Likely pathogenic ★ same condition
KERA p.Asn81Ser Likely pathogenic ★ same condition
KERA p.Gly111Arg Uncertain significance ★ ⚠ same condition
KERA p.Pro208Arg Uncertain significance ★ ⚠ same condition
KERA p.Tyr77His 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/kera-p-val23 (accessed [today's date]).

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