Is SLC19A1 p.Ala368Val (c.1103C>T) pathogenic?

SLC19A1 p.Ala368Val (c.1103C>T) is classified Uncertain significance in SLC19A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-09). AlphaMissense: likely benign (0.1852); Very rare (popmax 0.00273%, afr).

How common is SLC19A1 p.Ala368Val (c.1103C>T) in the general population?

SLC19A1 p.Ala368Val (c.1103C>T) is very rare (popmax 0.00273%, afr) (gnomAD).

What do computational predictors say about SLC19A1 p.Ala368Val (c.1103C>T)?

AlphaMissense predicts likely benign (score 0.1852) — an in-silico prediction, not a clinical call.

SLC19A1 p.Ala368Val

c.1103C>T · rs2077851310 · VCV2988504

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1852 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00273%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1852	likely benign
REVEL	0.59	indeterminate
SaProt	LLR -12.35	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP -3.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.89 · regional, not allelic
Overall
CADD	24.5	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 0.00273% African / African-American · 2/73,142 alleles

Filtering AF 0.000454% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00017%

Overall 0.000128% 2/1,560,832 alleles · very rare exomes 2/1,408,576 · genomes 0/152,256 · joint denominator

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: SLC19A1
Protein: p.Ala368Val
Coding: c.1103C>T
MANE Select: NM_194255
dbSNP: rs2077851310
Type: single nucleotide variant
Location: chr21:45530818 (GRCh38)
Gene constraint: LOEUF 1.585 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.30 · 19 PDB
Residue 368: an α-helix

Full SLC19A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL18A1 p.Arg1081Ter Pathogenic/Likely pathogenic ★★ same type
COL18A1 p.Arg915Ter Pathogenic/Likely pathogenic ★★ same type
RFC1 p.Arg383Ter Pathogenic/Likely pathogenic ★★ same type
COL18A1 c.*30G>A Uncertain significance ★★ same type
COL18A1 p.Ala1089Thr Uncertain significance ★★ ⚠ same type
COL18A1 p.Ala1254Val Uncertain significance ★★ ⚠ same type
COL18A1 p.Arg1081Gln Uncertain significance ★★ ⚠ same type
COL18A1 p.Arg1183His 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/slc19a1-p-ala368val (accessed [today's date]).

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