Is KERA p.Arg313Ter (c.937C>T) pathogenic?

KERA p.Arg313Ter (c.937C>T) is classified Pathogenic in KERA (ClinVar, Single submitter, 2 submitters; last evaluated 2024-09-22). Very rare (popmax 0.00167%, amr); Associated with cornea plana 2.

What condition is associated with KERA p.Arg313Ter (c.937C>T)?

KERA p.Arg313Ter (c.937C>T) is associated with cornea plana 2 (ClinVar).

How common is KERA p.Arg313Ter (c.937C>T) in the general population?

KERA p.Arg313Ter (c.937C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

KERA p.Arg313Ter

c.937C>T · rs121917863 · VCV6522

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

cornea plana 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.22	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 9.1	GERP 1.8, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,710 alleles

Filtering AF 0.000804% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000651%

Overall 0.00124% 20/1,610,592 alleles · very rare exomes 18/1,458,984 · genomes 2/151,608 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00469%	21,315
Admixed Americangrpmax	0.00167%	59,710
European (non-Finnish)	0.00136%	73,604

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.Arg313Ter
Coding: c.937C>T
MANE Select: NM_007035
dbSNP: rs121917863
Type: single nucleotide variant
Location: chr12:91051468 (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.Arg313Gln Likely benign ★ same residue
KERA p.Arg279Ter Pathogenic ★★ same condition
KERA p.Asn247Ser Pathogenic ★★ same condition
KERA p.Val23= Benign ★★ 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

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-arg313ter (accessed [today's date]).

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