Is MERTK p.Val469Phe (c.1405G>T) pathogenic?

MERTK p.Val469Phe (c.1405G>T) is classified Conflicting classifications of pathogenicity in MERTK (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2023-10-01). AlphaMissense: likely benign (0.1047); Rare (popmax 0.158%, eas); Associated with inherited retinal dystrophy.

What condition is associated with MERTK p.Val469Phe (c.1405G>T)?

MERTK p.Val469Phe (c.1405G>T) is associated with inherited retinal dystrophy, retinitis pigmentosa (ClinVar).

How common is MERTK p.Val469Phe (c.1405G>T) in the general population?

MERTK p.Val469Phe (c.1405G>T) is rare (popmax 0.158%, eas) (gnomAD).

What do computational predictors say about MERTK p.Val469Phe (c.1405G>T)?

AlphaMissense predicts likely benign (score 0.1047) — an in-silico prediction, not a clinical call.

MERTK p.Val469Phe

c.1405G>T · rs79943145 · VCV330755

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1047 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.158%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.1047	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -10.54	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP -2.3
Regional constraint	o/e 0.90	unconstrained · MANE · 130 kb · p 0.00043 · regional, not allelic
Overall
CADD	11.74	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 0.158% East Asian · 71/44,876 alleles

Filtering AF 0.129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.118%

Overall 0.00446% 72/1,614,200 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.158%	632
European (non-Finnish)	8.47e-05%	1,180,036

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.Val469Phe
Coding: c.1405G>T
MANE Select: NM_006343
dbSNP: rs79943145
Type: single nucleotide variant
Location: chr2:111994359 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB
Residue 469: the fibronectin type-iii 2 domain

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa

Similar variants

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.Arg727Ter Pathogenic ★★ same condition
MERTK p.Arg732Ter 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-val469phe (accessed [today's date]).

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