Is MERTK p.Pro313Leu (c.938C>T) pathogenic?

MERTK p.Pro313Leu (c.938C>T) is classified Uncertain significance in MERTK (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-02). AlphaMissense: likely benign (0.0739); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with MERTK p.Pro313Leu (c.938C>T)?

MERTK p.Pro313Leu (c.938C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MERTK p.Pro313Leu (c.938C>T) in the general population?

MERTK p.Pro313Leu (c.938C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about MERTK p.Pro313Leu (c.938C>T)?

AlphaMissense predicts likely benign (score 0.0739) — an in-silico prediction, not a clinical call.

MERTK p.Pro313Leu

c.938C>T · rs780578672 · VCV1946529

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0739 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0739	likely benign
REVEL	0.399	indeterminate
SaProt	LLR -10.06	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 1.8	GERP 0.49, phastCons 0.053
Regional constraint	o/e 0.90	unconstrained · MANE · 130 kb · p 0.00043 · regional, not allelic
Overall
CADD	22.1	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 0.005% Admixed American · 3/59,972 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000806% 13/1,613,474 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,991
South Asian	0.00439%	22,765
Remaining individualsnot grpmax-eligible	0.0032%	31,235
African / African-American	0.00267%	37,429
European (non-Finnish)	0.00017%	589,821

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.Pro313Leu
Coding: c.938C>T
MANE Select: NM_006343
dbSNP: rs780578672
Type: single nucleotide variant
Location: chr2:111968230 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB
Residue 313: the fibronectin type-iii 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

Similar variants

MERTK p.Pro313= Likely benign ★★ same residue
MERTK p.Pro313Arg Uncertain significance ★ ⚠ same residue
MERTK p.Ala29Gly Uncertain significance ★★ ⚠ same condition
MERTK p.Ala353Val Uncertain significance ★★ ⚠ same condition
MERTK p.Ala773Thr Uncertain significance ★★ ⚠ same condition
MERTK p.Ala944Thr Uncertain significance ★★ ⚠ same condition
MERTK p.Arg237Cys Uncertain significance ★★ ⚠ same condition
MERTK p.Arg557Gln Uncertain significance ★★ ⚠ 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-pro313leu (accessed [today's date]).

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