Is MERTK p.Ser172Trp (c.515C>G) pathogenic?

MERTK p.Ser172Trp (c.515C>G) is classified Uncertain significance in MERTK (ClinVar, Multiple submitters, 4 submitters; last evaluated 2022-10-19). AlphaMissense: likely benign (0.1974); Very rare (popmax 0.00441%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MERTK p.Ser172Trp (c.515C>G)?

MERTK p.Ser172Trp (c.515C>G) is associated with Inborn genetic diseases, inherited retinal dystrophy (ClinVar).

How common is MERTK p.Ser172Trp (c.515C>G) in the general population?

MERTK p.Ser172Trp (c.515C>G) is very rare (popmax 0.00441%, nfe) (gnomAD).

What do computational predictors say about MERTK p.Ser172Trp (c.515C>G)?

AlphaMissense predicts likely benign (score 0.1974) — an in-silico prediction, not a clinical call.

MERTK p.Ser172Trp

c.515C>G · rs143570667 · VCV959719

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1974 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1974	likely benign
REVEL	0.375	indeterminate
SaProt	LLR -13.06	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 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 130 kb · p 0.00043 · regional, not allelic
Overall
CADD	24.8	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 0.00441% European (non-Finnish) · 52/1,179,768 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00328% 53/1,613,448 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00441%	22,688
Remaining individualsnot grpmax-eligible	0.0016%	62,454

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.Ser172Trp
Coding: c.515C>G
MANE Select: NM_006343
dbSNP: rs143570667
Type: single nucleotide variant
Location: chr2:111944992 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB
Residue 172: a disulfide bond; the ig-like c2-type 1 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: inherited retinal dystrophy

Similar variants

MERTK p.Ser172Leu Uncertain significance ★★ ⚠ same residue
MERTK c.2189+1G>T Pathogenic ★★ same condition
MERTK p.Ala768Thr Pathogenic/Likely pathogenic ★★ same condition
MERTK p.Arg651Ter Pathogenic ★★ same condition
MERTK p.Arg722Ter Pathogenic ★★ same condition
MERTK p.Arg727Ter Pathogenic ★★ same condition
MERTK p.Arg732Ter Pathogenic ★★ same condition
MERTK p.Arg775Ter 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-ser172trp (accessed [today's date]).

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