Is RAD18 p.Ser144Phe (c.431C>T) pathogenic?

RAD18 p.Ser144Phe (c.431C>T) is classified Uncertain significance in RAD18 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: likely benign (0.1032); Ultra-rare (popmax 0.0183%, nfe).

How common is RAD18 p.Ser144Phe (c.431C>T) in the general population?

RAD18 p.Ser144Phe (c.431C>T) is ultra-rare (popmax 0.0183%, nfe) (gnomAD).

What do computational predictors say about RAD18 p.Ser144Phe (c.431C>T)?

AlphaMissense predicts likely benign (score 0.1032) — an in-silico prediction, not a clinical call.

RAD18 p.Ser144Phe

c.431C>T · rs141788084 · VCV3151003

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1032 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1032	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -9.35	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 3.7	GERP 2.3, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 82 kb · p 0.055 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% European (non-Finnish) · 216/1,180,020 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0155%

Overall 0.0141% 228/1,613,986 alleles · ultra-rare exomes 217/1,461,862 · genomes 11/152,124 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0183%	5,463
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0112%	8,927
African / African-American	0.00401%	24,959
Finnishnot grpmax-eligible	0.00156%	64,042

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: RAD18
Protein: p.Ser144Phe
Coding: c.431C>T
MANE Select: NM_020165
dbSNP: rs141788084
Type: single nucleotide variant
Location: chr3:8941640 (GRCh38)
Gene constraint: LOEUF 1.05 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.69 · 8 PDB

Full RAD18 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RAD18 p.Ala101Gly Uncertain significance ★ ⚠ same type
RAD18 p.Ala163Val Uncertain significance ★ ⚠ same type
RAD18 p.Ala365Ser Uncertain significance ★ ⚠ same type
RAD18 p.Ala481Thr Uncertain significance ★ ⚠ same type
RAD18 p.Arg123Ser Uncertain significance ★ ⚠ same type
RAD18 p.Arg131Ser Uncertain significance ★ ⚠ same type
RAD18 p.Arg131Thr Uncertain significance ★ ⚠ same type
RAD18 p.Arg173His Uncertain significance ★ ⚠ same type

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/rad18-p-ser144phe (accessed [today's date]).

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