Is MERTK p.Val864Phe (c.2590G>T) pathogenic?

MERTK p.Val864Phe (c.2590G>T) is classified Conflicting classifications of pathogenicity in MERTK (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-01). AlphaMissense: likely benign (0.0864); Rare (popmax 0.28%, sas); Associated with retinitis pigmentosa.

What condition is associated with MERTK p.Val864Phe (c.2590G>T)?

MERTK p.Val864Phe (c.2590G>T) is associated with retinitis pigmentosa (ClinVar).

How common is MERTK p.Val864Phe (c.2590G>T) in the general population?

MERTK p.Val864Phe (c.2590G>T) is rare (popmax 0.28%, sas) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MERTK p.Val864Phe (c.2590G>T)?

AlphaMissense predicts likely benign (score 0.0864) — an in-silico prediction, not a clinical call.

MERTK p.Val864Phe

c.2590G>T · rs557004700 · VCV893541

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0864 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.28%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.0864	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -6.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -1.3, phastCons 0.007
Regional constraint	o/e 0.90	unconstrained · MANE · 130 kb · p 0.00043 · regional, not allelic
Overall
CADD	13.58	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

Grpmax group 0.28% South Asian · 255/91,090 alleles

Filtering AF 0.252% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.241%

Overall 0.0166% 268/1,614,132 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.28%	357
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.00333%	30,007
African / African-American	0.00133%	75,012
European (non-Finnish)	0.000169%	590,023

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: MERTK
Protein: p.Val864Phe
Coding: c.2590G>T
MANE Select: NM_006343
dbSNP: rs557004700
Type: single nucleotide variant
Location: chr2:112028454 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB

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

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

MERTK p.Val864Ile Uncertain significance ★★ ⚠ same residue
MERTK c.1296+1G>A Pathogenic/Likely pathogenic ★★ same condition
MERTK c.2189+1G>T Pathogenic ★★ same condition
MERTK p.Ala768Thr Pathogenic/Likely pathogenic ★★ same condition
MERTK p.Arg651Ter Pathogenic ★★ same condition
MERTK p.Arg687Ter Pathogenic/Likely pathogenic ★★ same condition
MERTK p.Arg722Ter Pathogenic ★★ same condition
MERTK p.Cys115Trp Pathogenic/Likely pathogenic ★★ 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/mertk-p-val864phe (accessed [today's date]).

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