Is MERTK p.Arg629Trp (c.1885C>T) pathogenic?

MERTK p.Arg629Trp (c.1885C>T) is classified Uncertain significance in MERTK (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-08-28). AlphaMissense: likely benign (0.1932); Very rare (popmax 0.00873%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MERTK p.Arg629Trp (c.1885C>T)?

MERTK p.Arg629Trp (c.1885C>T) is associated with Inborn genetic diseases, retinitis pigmentosa (ClinVar).

How common is MERTK p.Arg629Trp (c.1885C>T) in the general population?

MERTK p.Arg629Trp (c.1885C>T) is very rare (popmax 0.00873%, nfe) (gnomAD).

What do computational predictors say about MERTK p.Arg629Trp (c.1885C>T)?

AlphaMissense predicts likely benign (score 0.1932) — an in-silico prediction, not a clinical call.

MERTK p.Arg629Trp

c.1885C>T · rs749774293 · VCV892740

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1932 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00873%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1932	likely benign
REVEL	0.567	indeterminate
SaProt	LLR -11.25	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 130 kb · p 0.00043 · regional, not allelic
Overall
CADD	27.8	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 0.00873% European (non-Finnish) · 103/1,179,418 alleles

Filtering AF 0.00733% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00684%

Overall 0.00688% 111/1,613,314 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00873%	11,451
Remaining individualsnot grpmax-eligible	0.0048%	20,823
Finnishnot grpmax-eligible	0.00312%	32,004
African / African-American	0.00267%	37,440
South Asian	0.0011%	91,062

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.Arg629Trp
Coding: c.1885C>T
MANE Select: NM_006343
dbSNP: rs749774293
Type: single nucleotide variant
Location: chr2:112008400 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB
Residue 629: an α-helix; the protein kinase domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa

Similar variants

MERTK p.Arg629Gln 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-arg629trp (accessed [today's date]).

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