Is KERA p.Phe40= (c.120C>T) pathogenic?

KERA p.Phe40= (c.120C>T) is classified Likely benign in KERA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-15). Very rare (popmax 0.00223%, eas); Associated with KERA-related disorder.

What condition is associated with KERA p.Phe40= (c.120C>T)?

KERA p.Phe40= (c.120C>T) is associated with KERA-related disorder (ClinVar).

How common is KERA p.Phe40= (c.120C>T) in the general population?

KERA p.Phe40= (c.120C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

KERA p.Phe40=

c.120C>T · rs199813838 · VCV3057860

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

KERA-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.1	GERP -5.7
Overall
CADD	3.024	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,752 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00267% 43/1,610,304 alleles · very rare exomes 38/1,459,176 · genomes 5/151,128 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0141%	7,086
Remaining individualsnot grpmax-eligible	0.00963%	10,388
East Asiangrpmax	0.00223%	44,752
European (non-Finnish)	0.00204%	49,073
Admixed American	0.00168%	59,658
African / African-American	0.00134%	74,692
South Asian	0.0011%	90,962

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.Phe40=
Coding: c.120C>T
MANE Select: NM_007035
dbSNP: rs199813838
Type: single nucleotide variant
Location: chr12:91056162 (GRCh38)
Gene constraint: LOEUF 1.284 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.42
Residue 40: the lrrnt domain

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

Disease context

KERA-related disorder

Similar variants

KERA p.Asn247Ser Pathogenic ★★ same condition
KERA p.Ser256Ter Likely pathogenic ★ same condition
KERA p.Arg279Ter Pathogenic ★★ same type
KERA p.Arg323Cys Uncertain significance ★★ ⚠ same type
KERA p.Pro43His Uncertain significance ★★ ⚠ same type
KERA c.887-8C>T Benign ★★ same type
KERA p.Gln25= Benign ★★ same type
KERA p.Val23= Benign ★★ same type

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-phe40 (accessed [today's date]).

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